U.S. patent application number 11/548349 was filed with the patent office on 2007-06-14 for fab i inhibitor and process for preparing same.
Invention is credited to Joong Myung Cho, Young Lan Hyun, Cheol Min Kim, Seonggu Ro, Doug Gyu Shin.
Application Number | 20070135465 11/548349 |
Document ID | / |
Family ID | 37943021 |
Filed Date | 2007-06-14 |
United States Patent
Application |
20070135465 |
Kind Code |
A1 |
Kim; Cheol Min ; et
al. |
June 14, 2007 |
Fab I Inhibitor and Process for Preparing Same
Abstract
A compound which is effective for inhibiting Fab I, and a method
for treating a bacterial infection.
Inventors: |
Kim; Cheol Min; (Seoul,
KR) ; Shin; Doug Gyu; (Seoul, KR) ; Ro;
Seonggu; (Seoul, KR) ; Cho; Joong Myung;
(Seoul, KR) ; Hyun; Young Lan; (Seoul,
KR) |
Correspondence
Address: |
MORGAN & FINNEGAN, L.L.P.
3 WORLD FINANCIAL CENTER
NEW YORK
NY
10281-2101
US
|
Family ID: |
37943021 |
Appl. No.: |
11/548349 |
Filed: |
October 11, 2006 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
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60827029 |
Sep 26, 2006 |
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60726814 |
Oct 13, 2005 |
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Current U.S.
Class: |
514/269 ;
514/348; 544/309; 546/296 |
Current CPC
Class: |
C07D 213/69 20130101;
C07D 409/14 20130101; C07D 405/06 20130101; C07D 413/06 20130101;
C07D 213/74 20130101; C07D 405/14 20130101; C07D 237/16 20130101;
C07D 405/12 20130101; C07D 409/12 20130101; C07D 417/14 20130101;
C07D 213/64 20130101; C07D 417/06 20130101; C07D 239/52 20130101;
C07D 213/70 20130101; C07D 239/47 20130101; C07D 401/06 20130101;
C07D 413/12 20130101; C07D 401/12 20130101; C07D 413/14 20130101;
A61P 31/04 20180101 |
Class at
Publication: |
514/269 ;
514/348; 544/309; 546/296 |
International
Class: |
A61K 31/513 20060101
A61K031/513; A61K 31/4412 20060101 A61K031/4412; C07D 213/69
20060101 C07D213/69; C07D 239/46 20060101 C07D239/46 |
Claims
1. A compound having a formula selected from the group consisting
of formula (I), formula (II), and pharmaceutically acceptable
analogs thereof selected from the group consisting of salt, acid,
ester, amide, and nitrile: ##STR12## wherein, R.sub.1 is selected
from the group of radicals consisting of: (a) H, (b) C.sub.1-8
alkyl, C.sub.1-8 alkenyl, C.sub.1-8 alkynyl, (c) aryl, C.sub.3-8
cycloalkyl, C.sub.3-8 cycloalkenyl, (d) an analog of a radical of
group (c) containing one or more heteroatoms selected from N, S and
O, and (e) a substituted analog of a radical selected from the
group consisting of groups (b), (c), and (d), said substituted
analog containing one or more substituents selected from the group
consisting of: hydroxyl, halogen, C.sub.1-6 alkyl, C.sub.3-8
cycloalkyl, C.sub.3-8 heterocycloalkyl, alkyloxy, amino,
alkylamino, carboxyl, nitro, sulfonylamide, alkylsulfonyl, amide,
dioxoisoindole, trihaloalkyl, aryl, heteroaryl, substituted aryl,
and substituted heteroaryl, wherein said substituted aryl and
substituted heteroaryl contain one or more substituents selected
from the group consisting of C.sub.1-6 alkyl, C.sub.3-8 cycloalkyl,
C.sub.3-8 heterocycloalkyl, alkyloxy, amino, alkylamino, carboxyl,
nitro, sulfonylamide, alkylsulfonyl, amide, dioxoisoindole,
trihaloalkyl, and aryl; A is selected from the group consisting of
C--R.sub.2 and N; R.sub.2 is selected from the group consisting of
H, C.sub.1-5 alkyl, benzyl, and substituted C.sub.1-5 alkyl
containing one or more substituents selected from the group
consisting of methyl, ethyl, hydroxyl, hydroxylmethyl and
hydroxylethyl; B is selected from the group consisting of carbonyl,
CH.sub.2 and NH; R.sub.4 is selected from the group of radicals
consisting of: (a) C.sub.1-8 alkyl, C.sub.1-8 alkenyl, C.sub.1-8
alkynyl, (b) aryl, C.sub.3-8 cycloalkyl, C.sub.3-8 cycloalkenyl,
(c) an analog of a radical of group (b) containing one or more
heteroatoms selected from N, S and O. (d) a substituted analog of a
radical selected from the group consisting of groups (a), (b), and
(c), said substituted analog containing one or more substituents
selected from the group consisting of: hydroxyl, halogen, C.sub.1-6
alkyl, C.sub.3-8 cycloalkyl, C.sub.3-8 heterocycloalkyl, alkyloxy,
amino, alkylamino, carboxyl, nitro, sulfonylamide, alkylsulfonyl,
amide, dioxoisoindole, trihaloalkyl, aryl, heteroaryl, substituted
aryl, and substituted heteroaryl, wherein said substituted aryl and
substituted heteroaryl contain one or more substituents selected
from the group consisting of: C.sub.1-6 alkyl, C.sub.3-8
cycloalkyl, C.sub.3-8 heterocycloalkyl, alkyloxy, amino,
alkylamino, carboxyl, nitro, sulfonylamide, alkylsulfonyl, amide,
dioxoisoindole, trihaloalkyl, and aryl; W is selected from the
group consisting of C--R.sub.6 and N; Z is selected from the group
consisting of C--R.sub.5 and N; R.sub.5 and R.sub.6 are each
independently selected from the group consisting of H, halogen,
C.sub.1-5 alkyl, and substituted C.sub.1-5 alkyl containing one or
more substituents selected from the group consisting of methyl,
ethyl, hydroxyl, hydroxylmethyl and hydroxylethyl; and X is
selected from C, N, O and S.
2. The compound of claim 1 wherein the alkyl, alkenyl, and alkynyl
groups of R.sub.1, R.sub.2, R.sub.4, R.sub.5 and R.sub.6 are
linear.
3. The compound of claim 1 wherein the alkyl, alkenyl, and alkynyl
groups of R.sub.1, R.sub.2, R.sub.4, R.sub.5 and R.sub.6 are
branched.
4. The compound of claim 1, which is selected from the group
consisting of: 4-benzyloxy-1-(2-chloro-benzyl)-1H-pyridin-2-one;
4-benzyloxy-1-(4-chloro-benzyl)-1H-pyridin-2-one;
4-benzyloxy-1-(4-nitro-benzyl)-1H-pyridin-2-one;
4-benzyloxy-1-(2,5-dichloro-benzyl)-1H-pyridin-2-one;
4-benzyloxy-1-(2,4-dichloro-benzyl)-1H-pyridin-2-one;
4-benzyloxy-2-(4-methoxy-benzyloxy)-pyridine;
4-benzyloxy-1-(4-methoxy-benzyl)-1H-pyridin-2-one;
4-benzyloxy-2-(4-methyl-benzyloxy)-pyridine;
4-benzyloxy-1-(4-methyl-benzyl)-1H-pyridin-2-one;
4-benzyloxy-1-(6-chloro-pyridin-3-ylmethyl)-1H-pyridin-2-one;
4-benzyloxy-1-(3-chloro-benzyl)-1H-pyridin-2-one;
1-benzyl-4-benzyloxy-1H-pyridin-2-one;
1-(4-amino-benzyl)-4-benzyloxy-1H-pyridin-2-one;
1-(2,4-dichloro-benzyl)-4-hydroxy-1H-pyridin-2-one;
3-benzyl-1-(2,4-dichloro-benzyl)-4-hydroxy-1H-pyridin-2-one;
4-(biphenyl-4-ylmethoxy)-1-(2,4-dichloro-benzyl)-1H-pyridin-2-one;
1-(2,4-dichloro-benzyl)-4-(2,4-dichloro-benzyloxy)-1H-pyridin-2-one;
4-(2-chloro-benzyloxy)-1-(2,4-dichloro-benzyl)-1H-pyridin-2-one;
1-(2,4-dichloro-benzyl)-4-methoxy-1H-pyridin-2-one;
1-(2,4-dichloro-benzyl)-4-isopropoxy-1H-pyridin-2-one;
4-cyclohexylmethoxy-1-(2,4-dichloro-benzyl)-1H-pyridin-2-one;
1-(2,4-dichloro-benzyl)-4-propoxy-1H-pyridin-2-one;
1-(2,4-dichloro-benzyl)-4-isobutoxy-1H-pyridin-2-one;
4-butoxy-1-(2,4-dichloro-benzyl)-1H-pyridin-2-one;
1-(2,4-dichloro-benzyl)-4-octyloxy-1H-pyridin-2-one;
1-(2,4-dichloro-benzyl)-4-(4-methyl-pentoxy)-1H-pyridin-2-one;
4-(but-3-enyloxy)-1-(2,4-dichloro-benzyl)-1H-pyridin-2-one;
1-(2,4-dichloro-benzyl)-4-pentyloxy-1H-pyridin-2-one;
[1-(2,4-dichloro-benzyl)-2-oxo-1,2-dihydro-pyridin-4-yloxy]-acetic
acid ethylester;
1-(2,4-dichloro-benzyl)-4-(3-methyl-butoxy)-1H-pyridin-2-one;
1-benzyl-4-pentyloxy-1H-pyridin-2-one;
1-(2-chloro-benzyl)-4-pentyloxy-1H-pyridin-2-one;
4-pentyloxy-1-propyl-1H-pyridin-2-one;
1-butyl-4-pentyloxy-1H-pyridin-2-one;
1-isobutyl-4-pentyloxy-1H-pyridin-2-one;
1-(3-methyl-butyl)-4-pentyloxy-1H-pyridin-2-one;
1-(2,4-dichloro-benzyl)-4-hexyloxy-1H-pyridin-2-one;
1-(2,4-dichloro-benzyl)-4-heptyloxy-1H-pyridin-2-one;
1-(4-chloro-benzyl)-4-pentyloxy-1H-pyridin-2-one;
4-aryloxy-1-(2,4-dichloro-benzyl)-1H-pyridin-2-one;
1-(2,4-dichloro-benzyl)-4-(3-methoxy-propoxy)-1H-pyridin-2-one;
1-(2,4-dichloro-benzyl)-4-(3-ethylamino-propoxy)-1H-pyridin-2-one;
1-(2,4-dichloro-benzyl)-4-(2-ethoxy-ethoxy)-1H-pyridin-2-one;
1-(3-methyl-but-2-enyl)-4-pentyloxy-1H-pyridin-2-one;
4-pentyloxy-1-thiazol-4-ylmethyl-1H-pyridin-2-one;
4-pentyloxy-1-pyridin-3-ylmethyl-1H-pyridin-2-one;
1-(2,4-dichloro-benzyl)-4-(4-methyl-pent-3-enyloxy)-1H-pyridin-2-one;
1-(2,4-dichloro-benzyl)-4-(3-methoxy-propoxy)-1H-pyridin-2-one;
1-(2,4-dichloro-benzyl)-4-phenetyloxy-1H-pyridin-2-one;
1-(2-methyl-benzyl)-4-pentyloxy-1H-pyridin-2-one;
4-pentyl-1-phenetyl-1H-pyridin-2-one;
1-(2,4-dichloro-5-fluoro-benzyl)-4-pentyloxy-1H-pyridin-2-one;
1-(3,4-dichloro-benzyl)-4-pentyloxy-1H-pyridin-2-one;
1-(3,4-difluoro-benzyl)-4-pentyloxy-1H-pyridin-2-one;
4-(4-benzyloxy-butoxy)-1-(2,4-dichloro-benzyl)-1H-pyridin-2-one;
1-(2,4-dichloro-benzyl)-4-(4-hydroxy-butoxy)-1H-pyridin-2-one;
4-(5-benzyloxy-pentyloxy)-1-(2,4-dichloro-benzyl)-1H-pyridin-2-one;
1-(2,4-dichloro-benzyl)-4-(5-hydroxy-pentyloxy)-1H-pyridin-2-one;
1-(6-chloro-benzo[1,3]dioxol-5-ylmethyl)-4-pentyloxy-1H-pyridin-2-one;
1-(2,4-dichloro-benzyl)-4-(2-methyl-benzyloxy)-1H-pyridin-2-one;
1-(2,4-dichloro-benzyl)-4-(4-methyl-benzyloxy)-1H-pyridin-2-one;
1-(2-nitro-benzyl)-4-pentyloxy-1H-pyridin-2-one;
1-(2-amino-benzyl)-4-pentyloxy-1H-pyridin-2-one;
N-[2-(2-oxo-4-pentyloxy-2H-pyridin-1-ylmethyl)-phenyl]-acetamide;
4-pentyloxy-1-(2-trifluoromethyl-benzyl)-1H-pyridin-2-one;
N-[4-(4-benzyloxy-2-oxo-2H-pyridin-1-ylmethyl)-phenyl]acetamide;
1-(2,4-dichloro-benzyl)-4-(naphthalen-2-ylmethoxy)-1H-pyridin-2-one;
1-naphthalen-2-ylmethyl-4-pentyloxy-1H-pyridin-2-one;
4-benzyloxy-1-(6-chloro-benzo[1,3]dioxol-5-ylmethyl)-1H-pyridin-2-one;
1-(6-chloro-benzo[1,3]dioxol-5-ylmethyl)-4-(3-methyl-butoxy)-1H-pyridin-2-
-one; 1-(2-methyl-benzyl)-4-(3-methyl-butoxy)-1H-pyridin-2-one;
4-(3-methyl-butoxy)-1-(2-nitro-benzyl)-1H-pyridin-2-one;
1-(2,4-dichloro-benzyl)-4-pentylamino-1H-pyridin-2-one;
1-(2,3-dichloro-benzyl)-4-pentyloxy-1H-pyridin-2-one;
1-(2-methoxy-benzyl)-4-pentyloxy-1H-pyridin-2-one;
1-(2,3-dimethoxy-benzyl)-4-pentyloxy-1H-pyridin-2-one;
4-(5-benzyloxy-pentyloxy)-1-(6-chloro-benzo[1,3]dioxol-5-ylmethyl)-1H-pyr-
idin-2-one;
1-(2-chloro-benzyl)-4-(3-methyl-butoxy)-1H-pyridin-2-one;
1-(3,4-dichloro-benzyl)-4-(3-methyl-butoxy)-1H-pyridin-2-one;
1-(2,4-dichloro-5-fluoro-benzyl)-4-(3-methyl-butoxy)-1H-pyridin-2-one;
1-benzyl-4-(3-methyl-butoxy)-1H-pyridin-2-one;
1-(4-chloro-benzyl)-4-(3-methyl-butoxy)-1H-pyridin-2-one;
1-(2,4-dichloro-benzyl)-4-pentyloxy-1H-pyrimidin-2-one;
1-(2,4-dichloro-benzyl)-4-(4-methyl-pentyloxy)-1H-pyrimidin-2-one;
1-(2,4-dichloro-benzyl)-4-phenoxy-1H-pyrimidin-2-one;
4-(butyl-methyl-amino)-1-(2,4-dichloro-benzyl)-1H-pyrimidin-2-one;
1-(2,4-dichloro-benzyl)-4-(2-diethylamino-ethoxy)-1H-pyrimidin-2-one;
4-butoxy-1-(2,4-dichloro-benzyl)-1H-pyrimidin-2-one;
1-(2,6-dichloro-benzyl)-4-pentyloxy-1H-pyridin-2-one;
1-(2-chloro-6-fluoro-benzyl)-4-pentyloxy-1H-pyridin-2-one;
1-(2-methyl-3-nitro-benzyl)-4-pentyloxy-1H-pyridin-2-one;
1-(3-amino-2-methyl-benzyl)-4-pentyloxy-1H-pyridin-2-one;
1-(4-methoxy-3,5-dimethyl-pyridin-2-ylmethyl)-4-pentyloxy-1H-pyridin-2-on-
e;
1-(6-chloro-benzo[1,3]dioxol-5-ylmethyl)-4-(5-hydroxy-pentyloxy)-1H-py-
ridin-2-one;
1-(2-methoxy-5-nitro-benzyl)-4-pentyloxy-1H-pyridin-2-one;
1-(5-amino-2-methoxy-benzyl)-4-pentyloxy-1H-pyridin-2-one;
1-(2-ethyl-benzyl)-4-pentyloxy-1H-pyridin-2-one;
1-(2-chloro-5-nitro-benzyl)-4-pentyloxy-1H-pyridin-2-one;
1-(5-amino-2-chloro-benzyl)-4-pentyloxy-1H-pyridin-2-one;
1-(4-methoxy-2,3-dimethyl-benzyl)-4-pentyloxy-1H-pyridin-2-one;
1-(2-methyl-pyridin-3-ylmethyl)-4-pentyloxy-1H-pyridin-2-one;
N-[4-chloro-3-(2-oxo-4-pentyloxy-2H-pyridin-1-ylmethyl)-phenyl]-acetamide-
;
1-(2,4-dichloro-benzyl)-4-(3-dimethylamino-propoxy)-1H-pyridin-2-one;
1-(2,4-dichloro-benzyl)-4-(4-dimethylamino-butoxy)-1H-pyridin-2-one;
1-(2,4-dichloro-benzyl)-4-(6-dimethylamino-hexyloxy)-1H-pyrimidin-2-one;
1-(2,4-dimethyl-benzyl)-4-pentyloxy-1H-pyridin-2-one;
1-(2-chloro-5-trifluoromethyl-benzyl)-4-pentyloxy-1H-pyridin-2-one;
1-(2-hydroxy-benzyl)-4-pentyloxy-1H-pyridin-2-one;
4-(3-cyclo-propoxy)-1-(2,4-dichloro-benzyl)-1H-pyrimidin-2-one;
1-(2,4-dichloro-benzyl)-4-(3-methyl-pentyloxy)-1H-pyrimidin-2-one;
1-(2,4-dichloro-benzyl)-4-hex-4-enyloxy-1H-pyrimidin-2-one;
4-(2-cyclopropyl-ethoxy)-1-(2,4-dichloro-benzyl)-1H-pyrimidin-2-one;
1-(2,4-dichloro-benzyl)-4-(3-methyl-pentyloxy)-1H-pyridin-2-one;
1-(2,4-dichloro-benzyl)-4-(5-morpholin-4-yl-pentyloxy)-1H-pyridin-2-one;
1-(2-chloro-5-methoxy-benzyl)-4-pentyloxy-1H-pyridin-2-one;
1-(2-chloro-5-ethoxy-benzyl)-4-pentyloxy-1H-pyridin-2-one;
1-(2-chloro-5-propoxy-benzyl)-4-pentyloxy-1H-pyridin-2-one;
1-[2-chloro-5-(2-hydroxy-ethoxy)-benzyl]-4-pentyloxy-1H-pyridin-2-one;
[4-chloro-3-(2-oxo-4-pentyloxy-2H-pyridin-1-ylmethyl)-oxy]-acetonitrile;
1-[5-(2-amino-ethoxy)-2-chloro-benzyl]-4-pentyloxy-1H-pyridin-2-one;
N-[2-methyl-3-(2-oxo-4-pentyloxy-2H-pyridin-1-ylmethyl)-phenyl]-acetamide-
; 1-(2-methyl-3-methylamino-benzyl)-4-phenyloxy-1H-pyridin-2-one;
1-(3-dimethylamino-2-methyl-benzyl)-4-phenyloxy-1H-pyridin-2-one;
1-(3-ethylamino-2-methyl-benzyl)-4-pentyloxy-1H-pyridin-2-one;
1-(3-diethylamino-2-methyl-benzyl)-4-pentyloxy-1H-pyridin-2-one;
1-(2-methyl-3-propylamino-benzyl)-4-pentyloxy-1H-pyridin-2-one;
1-(3-dipropylamino-2-methyl-benzyl)-4-pentyloxy-1H-pyridin-2-one;
1-[3-(2-hydroxy-ethylamino)-2-methyl-benzyl]-4-pentyloxy-1H-pyridin-2-one-
;
1-(2-chloro-5-methoxy-4-nitro-benzyl)-4-pentyloxy-1H-pyridin-2-one;
1-(4-amino-2-chloro-5-methoxy-benzyl)-4-pentyloxy-1H-pyridin-2-one;
N-[5-chloro-2-methoxy-4-(2-oxo-4-pentyloxy-2H-pyridin-1-ylmethyl)-phenyl]-
-acetamide;
1-(2-chloro-5-methoxy-4-methylamino-benzyl)-4-pentyloxy-1H-pyridin-2-one;
1-(2-chloro-4-dimethylamino-5-methoxy-benzyl)-4-pentyloxy-1H-pyridin-2-o-
ne;
1-(2-chloro-4-ethylamino-5-methoxy-benzyl)-4-pentyloxy-1H-pyridin-2-o-
ne;
1-(2-chloro-5-methoxy-4-propylamino-benzyl)-4-pentyloxy-1H-pyridin-2--
one;
1-[2-chloro-4-(2-hydroxy-ethylamino)-5-methoxy-benzyl]-4-pentyloxy-1-
H-pyridin-2-one;
1-(4-amino-6-chloro-3-methoxy-2-nitro-benzyl)-4-pentyloxy-1H-pyridin-2-on-
e;
1-(2,4-diamino-6-chloro-3-methoxy-benzyl)-4-pentyloxy-1H-pyridin-2-one-
;
1-(2,5-dichloro-6-methoxy-pyrimidin-4-ylmethyl)-4-pentyloxy-1H-pyridin--
2-one;
1-(2,4-dichloro-benzenesulfonyl)-4-pentyloxy-1H-pyridin-2-one;
1-(4-methanesulfonyl-benzyl)-4-pentyloxy-1H-pyridin-2-one;
1-(4-amino-2-chloro-5-hydroxy-benzyl)-4-pentyloxy-1H-pyridin-2-one;
4-(4-bromo-butoxy)-1-(2,4-dichloro-benzyl)-1H-pyridin-2-one;
4-[1-(2,4-dichloro-benzyl)-2-oxo-1,2-dihydro-pyridin-4-yloxy]-butylammoni-
um;
1-(5-chloro-2,6-dimethoxy-pyrimidin-4-ylmethyl)-4-pentyloxy-1H-pyridi-
n-2-one;
1-(2-amino-5-chloro-6-methoxy-pyrimidin-4-ylmethyl)-4-pentyloxy--
1H-pyridin-2-one;
1-(6-amino-2,5-dichloro-pyrimidin-4-ylmethyl)-4-pentyloxy-1H-pyridin-2-on-
e;
5-chloro-6-(2-oxo-4-pentyloxy-2H-pyridin-1-ylmethyl)-3H-benzoxazole-2--
one; 1-(2-chloro-4-hydroxy-benzyl)-4-pentyloxy-1H-pyridin-2-one;
1-(2-chloro-4-isopropoxy-benzyl)-4-pentyloxy-1H-pyridin-2-one;
2-[3-(2-oxo-4-pentyloxy-2H-pyridin-1-yl)-propyl]-isoindole-1,3-dione;
1-(3-amino-propyl)-4-pentyloxy-1H-pyridin-2-one;
N-[3-(2-oxo-4-pentyloxy-2H-pyridin-1-yl)-propyl]-acetamide;
1-(3-dimethylamino-propyl)-4-pentyloxy-1H-pyridin-2-one;
1-(2,4-dichloro-benzyl)-6-methyl-4-pentyloxy-1H-pyridin-2-one;
1-(2,4-dichloro-benzyl)-6-methyl-3-pentyl-4-pentyloxy-1H-pyridin-2-one;
1-(2-amino-ethyl)-4-pentyloxy-1H-pyridin-2-one;
N-[2-(2-oxo-4-pentyloxy-2H-pyridin-1-yl)-ethyl]-acetamide;
N-[1,1-dimethyl-2-(2-oxo-4-pentyloxy-2H-pyridin-1-yl)-ethyl]methanesulfon-
amide;
N-[1-(2-oxo-4-pentyloxy-2H-pyridin-1-ylmethyl)-propyl]-methanesulf-
onamide;
1-(7-nitro-benzo[1,3]dioxol-5-ylmethyl)-4-pentyloxy-1H-pyridin-2-
-one; 1-(2-chloro-3-nitro-benzyl)-4-pentyloxy-1H-pyridin-2-one;
1-(3-amino-2-chloro-benzyl)-4-pentyloxy-1H-pyridin-2-one;
N-[2-chloro-3-(2-oxo-4-pentyloxy-2H-pyridin-1-ylmethyl)-phenyl]-acetamide-
;
N-[2-chloro-3-(2-oxo-4-pentyloxy-2H-pyridin-1-ylmethyl)-phenyl]-methane-
sulfonamide;
N,N'-[2-chloro-3-(2-oxo-4-pentyloxy-2H-pyridin-1-ylmethyl)-phenyl]-dimeth-
anesulfonamide;
1-[2-chloro-3-(2-hydroxy-ethylamino)-benzyl]-4-pentyloxy-1H-pyridin-2-one-
; 4-chloro-2-(2-chloro-benzyl)-5-pentyloxy-2H-pyridazin-3-one;
2-(2-chloro-benzyl)-5-pentyloxy-2H-pyridazin-3-one;
1-(3-amino-2,6-dichloro-benzyl)-4-pentyloxy-1H-pyridin-2-one;
1-(3-benzyloxy-2-chloro-4-methoxy-benzyl)-4-pentyloxy-1H-pyridin-2-one;
1-(2-chloro-3,4-dimethoxy-benzyl)-4-pentyloxy-1H-pyridin-2-one;
1-(2-chloro-3-hydroxy-4-methoxy-benzyl)-4-pentyloxy-1H-pyridin-2-one;
1-[2-chloro-4-methoxy-3-(2-methoxy-ethoxy)-benzyl]-4-pentyloxy-1H-pyridin-
-2-one;
1-[2-chloro-4-methoxy-3-(2-pyrrolidin-1-yl-ethoxy)-benzyl]-4-pent-
yloxy-1H-pyridin-2-one;
1-[2-chloro-3-(2-dimethylamino-ethoxy)-4-methoxy-benzyl]-4-pentyloxy-1H-p-
yridin-2-one;
2-{3-[2-chloro-6-methoxy-3-(2-oxo-4-pentyloxy-2H-pyridin-1-ylmethyl)-phen-
oxyl]-propyl}-isoindole-1,3-dione;
1-[3-(2-dimethylamino-ethoxy)-2-methyl-benzyl]-4-pentyloxy-1H-pyridin-2-o-
ne;
1-[2-chloro-3-(2-dimethylamino-ethylamino)-benzyl]-4-pentyloxy-1H-pyr-
idin-2-one;
1-[2,6-dichloro-3-(2-hydroxy-ethylamino)-benzyl]-4-pentyloxy-1H-pyridin-2-
-one;
1-[2,6-dichloro-3-(2-dimethylamino-ethylamino)-benzyl]-4-pentyloxy--
1H-pyridin-2-one;
1-[2,6-dichloro-3-(3-hydroxy-propylamino)-benzyl]-4-pentyloxy-1H-pyridin--
2-one;
1-[2,6-dichloro-3-(3dimethylamino-propylamino)-benzyl]-4-pentyloxy-
-1H-pyridin-2-one;
1-[3-(3-amino-propylamino)-2,6-dichloro-benzyl]-4-pentyloxy-1H-pyridin-2--
one; 1-(3-fluoro-2-methyl-benzyl)-4-pentyloxy-1H-pyridin-2-one;
1-(2-chloro-3-dimethylaminomethyl-4-fluoro-benzyl)-4-pentyloxy-1H-pyridin-
-2-one;
1-(2,6-dichloro-3-methylamino-benzyl)-4-pentyloxy-1H-pyridin-2-on-
e;
1-(2,6-dichloro-3-dimethylamino-benzyl)-4-pentyloxy-1H-pyridin-2-one;
[2-chloro-3-(2-oxo-4-pentyloxy-2H-pyridin-1-ylmethyl)-phenylamino]-acetic
acid;
1-(6-chloro-benzo[1,3]dioxol-5-ylmethyl)-4-(pyridin-4-ylmethoxy)-1-
H-pyridin-2-one;
1-(6-chloro-benzo[1,3]dioxol-5-ylmethyl)-4-(6-chloro-pyridin-3-ylmethoxy)-
-1H-pyridin-2-one;
1-(6-chloro-benzo[1,3]dioxol-5-ylmethyl)-4-(4-methoxy-3,5-dimethylpyridin-
-2-ylmethoxy)-1H-pyridin-2-one;
1-(6-chloro-benzo[1,3]dioxol-5-ylmethyl)-4-(2-methyl-pyridin-3-ylmethoxy)-
-1H-pyridin-2-one;
1-(6-chloro-benzo[1,3]dioxol-5-ylmethyl)-4-(thiazol-4-ylmethoxy)-1H-pyrid-
in-2-one;
1-(6-chloro-benzo[1,3]dioxol-5-ylmethyl)-4-(pyridin-2-ylmethoxy-
)-1H-pyridin-2-one; pentanoic acid
1-(6-chloro-benzo[1,3]dioxol-5-ylmethyl)-2-oxo-1,2-dihydro-pyridin-4-yl
ester; hexanoic acid
1-(6-chloro-benzo[1,3]dioxol-5-ylmethyl)-2-oxo-1,2-dihydro-pyridin-4-yl
ester;
1-(2-chloro-3-trifluoromethyl-benzyl)-4-pentyloxy-1H-pyridin-2-on-
e; thiophene-2-carboxyl acid
1-(6-chloro-benzo[1,3]dioxol-5-ylmethyl)-2-oxo-1,2-dihydro-pyridin-4-yl
ester; toluene-4-sulfonic acid
1-(6-chloro-benzo[1,3]dioxol-5-ylmethyl)-2-oxo-1,2-dihydro-pyridin-4-yl
ester;
1-(6-chloro-benzo[1,3]dioxol-5-ylmethyl)-4-(4,4,5,5,5-pentafluoro-
-pentyloxy)-1H-pyridin-2-one;
1-(6-chloro-benzo[1,3]dioxol-5-ylmethyl)-4-(2-dimethylamino-ethoxy)-1H-py-
ridin-2-one;
1-(2,4-dichloro-benzyl)-4-(5-fluoro-pentyloxy)-1H-pyridin-2-one;
3-[1-(2,4-dichloro-benzyl)-2-oxo-1,2-dihydro-pyridin-4-yloxymethyl]-indol-
e-1-carboxyl acid tetra-butyl ester;
1-(2,4-dichloro-benzyl)-4-(2-thiophen-2-yl-ethoxy)-1H-pyridin-2-one;
1-(2,4-dichloro-benzyl)-4-(2-thiophen-3-yl-ethoxy)-1H-pyridin-2-one;
1-(2,4-dichloro-benzyl)-4-(2-pyrrol-1-yl-ethoxy)-1H-pyridin-2-one;
1-(2,4-dichloro-benzyl)-4-(3-pyrrol-1-yl-propoxy)-1H-pyridin-2-one;
1-(3-amino-2-methyl-benzyl)-4-(2-thiophen-2-yl-ethoxy)-1H-pyridin-2-one;
1-(3-amino-2-methyl-benzyl)-4-(2-pyrrol-1-yl-ethoxy)-1H-pyridin-2-one;
1-(3-amino-2-methyl-benzyl)-4-[2-(4-methyl-thiazol-5-yl)-ethoxy]-1H-pyrid-
in-2-one;
1-(3-amino-2-methyl-benzyl)-4-(2-(5-bromothiophen-2-yl)-ethoxy)-
-1H-pyridin-2-one;
1-(3-amino-2-methyl-benzyl)-4-(2-(5-fluorothiophen-2-yl)-ethoxy)-1H-pyrid-
in-2-one;
1-[3-(2-hydroxy-ethylamino)-2-methyl-benzyl]-4-(2-thiophen-2-yl-
-ethoxy)-1H-pyridin-2-one;
2-{2-methyl-3-[2-oxo-4-(2-thiophene-2-yl-ethoxy)-2H-pyridin-1-ylmethyl]-p-
henylamino}-acetamide;
1-[3-(cyclopropylmethyl-amino)-2-methyl-benzyl]-4-(2-thiophen-2-yl-ethoxy-
)-1H-pyridin-2-one;
N-{2-methyl-3-[2-oxo-4-(2-thiophen-2-yl-ethoxy)-2H-pyridin-1-ylmethyl]-ph-
enylamino}-acetonitrile;
N-(2-{2-methyl-3-[2-oxo-4-(2-thiophen-2-yl-ethoxy)-2H-pyridin-1-ylmethyl]-
-phenylamino}-ethyl)-acetamide;
1-[2-methyl-3-(2-pyrrol-1-yl-ethylamino)-benzyl]-4-(2-thiophen-2-yl-ethox-
y)-1H-pyridin-2-one;
1-[2-methyl-3-(2-oxo-2-pyrrolidin-1-yl-ethylamino)-benzyl]-4-(2-thiophen--
2-yl-ethoxy)-1H-pyridin-2-one;
1-[2-methyl-3-(2-oxo-2-piperidin-1-yl-ethylamino)-benzyl]-4-(2-thiophen-2-
-yl-ethoxy)-1H-pyridin-2-one;
N,N-dimethyl-2-{2-methyl-3-[2-oxo-4-(2-thiophen-2-yl-ethoxy)-2H-pyridin-1-
-ylmethyl]-phenylamino}-acetamide;
1-{2-methyl-3-[2-(4-methyl-piperazin-1-yl)-2-oxo-ethylamino]-benzyl}-4-(2-
-thiophen-2-yl-ethoxy)-1H-pyridin-2-one;
1-[2-methyl-3-(2-morpholin-4-yl-2-oxo-ethylamino)-benzyl]-4-(2-thiophen-2-
-yl-ethoxy)-1H-pyridin-2-one;
1-(3-amino-2-methyl-benzyl)-4-(2-furan-2-yl-ethoxy)-1H-pyridin-2-one;
1-(3-amino-2-methyl-benzyl)-4-[2-(5-methyl-thiophen-2-yl)-ethoxy]-1H-pyri-
din-2-one;
1-(3-amino-2-methyl-benzyl)-4-[2-(5-chloro-thiophen-2-yl)-ethoxy]-1H-pyri-
din-2-one;
1-(2,4-dichloro-benzyl)-4-[2-(3-methyl-thiophen-2-yl)-ethoxy]-1H-pyridin--
2-one;
1-(3-amino-2-methyl-benzyl)-4-(2-benzo[b]thiophen-3-yl-ethoxy)-1H--
pyridin-2-one;
1-(3-amino-2-methyl-benzyl)-4-[2-(5-chloro-3-methyl-benzo[b]thiophen-2-yl-
)-ethoxy]-1H-pyridin-2-one;
1-(3-amino-2-methyl-benzyl)-4-[2-(3-methyl-benzo[b]thiophen-2-yl)-ethoxy]-
-1H-pyridin-2-one;
1-(3-amino-2-methyl-benzyl)-4-[2-(5-methyl-furan-2-yl)-ethoxy]-1H-pyridin-
-2-one;
1-(3-amino-2-methyl-benzyl)-4-[2-(5-ethyl-furan-2-yl)-ethoxy]-1H--
pyridin-2-one;
5-[1-(3-amino-2-methyl-benzyl)-2-oxo-1,2-dihydro-pyridin-4-yloxymethyl]-f-
uran-2-carboxylic acid ethyl ester;
1-[3-(2-dimethylamino-ethylamino)-2-methyl-benzyl]-4-(2-thiophen-2-yl-eth-
oxy)-1H-pyridin-2-one;
1-(3-amino-2-methyl-benzyl)-4-[2-(5-methylsulfanyl-thiophen-2-yl)-ethoxy]-
-1H-pyridin-2-one;
1-(3-amino-2-methyl-benzyl)-4-(2-benzofuran-2-yl-ethoxy)-1H-pyridin-2-one-
;
1-(3-amino-2-methyl-benzyl)-4-[2-(3-methyl-isoxazol-5-yl)-ethoxy]-1H-py-
ridin-2-one;
1-(3-amino-2-methyl-benzyl)-4-[2-(4,5-dimethyl-thiophen-2-yl)-ethoxy]-1H--
pyridin-2-one;
1-(3-amino-2-methyl-benzyl)-4-[2-(5-ethyl-thiophen-2-yl)-ethoxy]-1H-pyrid-
in-2-one;
1-(3-amino-2,6-dichloro-benzyl)-4-(2-thiophen-2-yl-ethoxy)-1H-p-
yridin-2-one;
N-{2-methyl-3-[2-oxo-4-(2-thiophen-2-yl-ethoxy)-2H-pyridin-1-ylmethyl]-ph-
enyl}-acetamide;
1-[2-methyl-3-(2-piperidin-1-yl-ethylamino)-benzyl]-4-(2-thiophen-2-yl-et-
hoxy)-1H-pyridin-2-one;
1-[2-methyl-3-(2-morpholin-4-yl-ethylamino)-benzyl]-4-(2-thiophen-2-yl-et-
hoxy)-1H-pyridin-2-one;
N-{2-methyl-3-[2-oxo-4-(2-thiophen-2-yl-ethoxy)-2H-pyridin-1-ylmethyl]-ph-
enyl}-methanesulfonamide;
1-(3-amino-2-methyl-benzyl)-4-[2-(4-bromo-thiophen-2-yl)-ethoxy]-1H-pyrid-
in-2-one;
1-(6-chloro-benzo[1,3]dioxol-5-ylmethyl)-4-(2-pyrrol-1-yl-ethox-
y)-1H-pyridin-2-one;
1-(6-chloro-benzo[1,3]dioxol-5-ylmethyl)-4-(2-thiophen-2-yl-ethoxy)-1H-py-
ridin-2-one;
1-[2-methyl-3-(2-pyrrolidin-1-yl-ethylamino)-benzyl]-4-(2-thiophen-2-yl-e-
thoxy)-1H-pyridin-2-one;
N-(2-{2-methyl-3-[2-oxo-4-(2-thiophen-2-yl-ethoxy)-2H-pyridin-1-ylmethyl]-
-phenylamino}-ethyl)-acetamide;
1-{2-methyl-3-[(pyridin-3-ylmethyl)-amino]-benzyl}-4-(2-thiophen-2-yl-eth-
oxy)-1H-pyridin-2-one;
2-methyl-3-[2-oxo-4-(2-thiophen-2-yl-ethoxy)-2H-pyridin-1-ylmethyl]-pheny-
l ester;
1-{2-methyl-3-[(pyridin-4-ylmethyl)-amino]-benzyl}-4-(2-thiophen-
-2-yl-ethoxy)-1H-pyridin-2-one;
1-{2-methyl-3-[(thiazol-4-ylmethyl)-amino]-benzyl}-4-(2-thiophen-2-yl-eth-
oxy)-1H-pyridin-2-one;
1-[3-(4-methoxy-benzyloxy)-2-methyl-benzyl]-4-(2-thiophen-2-yl-ethoxy)-1H-
-pyridin-2-one;
1-{3-[(3,5-dimethyl-isoxazol-4-ylmethyl)-amino]-2-methyl-benzyl}-4-(2-thi-
ophen-2-yl-ethoxy)-1H-pyridin-2-one;
1-(3-hydroxy-2-methyl-benzyl)-4-(2-thiophen-2-yl-ethoxy)-1H-pyridin-2-one-
;
1-{2-methyl-3-[(1-methyl-pyrrolidin-2-ylmethyl)-amino]-benzyl}-4-(2-thi-
ophen-2-yl-ethoxy)-1H-pyridin-2-one;
1-{2-methyl-3-[2-(1-methyl-pyrrolidin-2-yl)-ethylamino]-benzyl}-4-(2-thio-
phen-2-yl-ethoxy)-1H-pyridin-2-one;
(2-{2-methyl-3-[2-oxo-4-(2-thiophen-2-yl-ethoxy)-2H-pyridin-1-ylmethyl]-p-
henylamino}-ethyl)-phosphonic acid diethyl ester;
4-(isobuthylthio)-1-(2-methyl-3-nitrobenzyl)pyridine-2(1H)-one;
1-(3-amino-2-methylbenzyl)-4-(isobutylthio)pyridine-2(1H)-one;
1-(3-amino-2-methylbenzyl)-4-(furan-2-ylmethylthio)pyridine-2(1H)-one;
1-(3-amino-2-methylbenzyl)-4-(pentylthio)pyridine-2-(1H)-one;
1-(3-amino-2-methylbenzyl)-4-(phenethylthio)pyridine-2(1H)-one;
1-(3-amino-2-methylbenzyl)-4-(butylthio)pyridine-2(1H)-one;
1-(3-amino-2-methylbenzyl)-4-(thiophen-2-ylmethylthio)pyridine-2(1H)-one;
1-(3-amino-2-methylbenzyl)-4-(pentylthio)pyridine-2(1H)-one;
1-(3-amino-2-methylbenzyl)-4-(propylthio)pyridine-2(1H)-one;
1-(3-amino-2-methylbenzyl)-4-(1-methylbutylthio)pyridine-2(1H)-one;
N,N-dimethyl-3-(2-methyl-3-((2-oxo-4-(2-(thiophen-2-yl)ethoxy)pyridin-1(2-
H)-yl)methyl)phenylamino)propane-1-sulfonamide;
1-(3-amino-2-methylbenzyl)-4-(2-(thiophene-2-yl)ethylamino)pyridine-2-(1H-
)-one.
5. A method of preparing the compound of claim 1 comprising:
forming a solution of a pyridone or pyridazine derivative
comprising an alcohol or amine functionality and NaH or potassium
t-butoxide in DMF; combining said solution with a halide compound
of the formula k-m-h where h is chloride or bromide; m is benzyl,
benzyloxy, or ylmethyl; and k is 2-chloro, 3-chloro, 4-chloro,
4-nitro, 2,5-dichloro, 2,4-dichloro, 4-menthoxy, 4-methyl, or
6-chloro-pyridin-3-, or 4-amino; stirring said combination for 30
minutes at room temperature to form a reaction product which
includes one or more of the compounds described in claim 1.
6. The method of claim 5 and further comprising: isolating said one
or more compounds described in claim 1 from said reaction product
by column chromatography.
7. A method of claim 6 and further comprising: hydrogenating said
isolated product with Pd/C to form a compound having a hydroxyl
substituent.
8. A method of claim 7 and further comprising: substituting said
hydroxyl substitutent by a radical selected from the group
consisting of (a) H; (b) C.sub.1-8 alkyl, C.sub.1-8 alkenyl,
C.sub.1-8 alkynyl; (c) aryl, C.sub.3-8 cycloalkyl or C.sub.3-8
cycloalkenyl; (d) an analog of the radicals of group b containing
one or more heteroatoms selected from N, S or O; and (e) a
substituted analog of a member of groups (b), (c), and (d), said
substituted analog containing one or more substituents selected
from the group consisting of hydroxyl, halogen, C.sub.1-6 alkyl,
C.sub.3-8 cycloalkyl, C.sub.3-8 heterocycloalkyl, alkyloxy, amino,
alkylamino, carboxyl, nitro, sulfonylamide, alkylsulfonyl, amide,
dioxoisoindole, trihaloalkyl, aryl and heteroaryl.
9. An anti-bacterial composition comprising the compound of claim 1
as an active ingredient.
10. The anti-bacterial composition of claim 9, which is in the form
of a formulation comprising the compound of claim 1 in the range of
50 to 5,000 mg, the formulation being selected from the group
consisting of oral, sublingual, inhalation, topical, rectal, and
injection formulations.
11. The anti-bacterial composition of claim 10, which is in the
form of a formulation comprising the compound of claim 1 in the
range of 150 to 3,000 mg.
12. The anti-bacterial composition of claim 10, which is in the
form of a formulation comprising the compound of claim 1 in the
range of 50 to 2,000 mg.
13. A method for inhibiting the activity of Fab I, wherein the
method comprises administering to a human in need thereof, an
effective amount of a compound of claim 1.
14. A method for treating bacteria-related disease, wherein the
method comprises administering to a human in need thereof, an
effective amount of a formulation of claim 10.
15. The method of claim 14, wherein said formulation is in the form
of a tablet, capsule or pill.
16. The method of claim 14, wherein the administration is by
subcutaneous, intravenous, intramuscular, intra-articular,
intra-synovial, intrasternal, intrathecal, intrahepatic,
intralesional and intracranial injection.
17. A kit for use in the treatment of bacteria-related disease
which comprises: (a) the formulation of claim 10 and (b) a
syringe.
18. A kit for use in a method of treating bacteria-related disease
comprising the formulation of claim 10 in the form of a powder,
granules, or concentrate and a solvent for reconstituting said
pharmaceutical composition to provide an oral dosage form.
19. A compound of claim 1 wherein X is O.
20. A compound of claim 19 wherein, A is CH; B is CH.sub.2; Z is
CH; and W is CH.
21. A compound of claim 19 wherein, A is CH; B is CH.sub.2; Z is
CH; and W is N.
22. A compound of claim 19 wherein: A is CH; B is CH.sub.2; W is
CH; and Z is N.
23. A compound of claim 20 wherein, R.sub.4 is selected from the
group consisting of: aryl and a substituted aryl containing one or
more substituents selected from the group consisting of hydroxyl,
halogen, C.sub.1-6 alkyl, C.sub.3-8 cycloalkyl, C.sub.3-8
heterocycloalkyl, alkyloxy, amino, alkylamino, carboxyl, nitro,
sulfonylamide, alkylsulfonyl, amide, dioxoisoindole, trihaloalkyl,
and aryl.
24. The compound of claim 23, wherein R.sub.1 is selected from the
group of radicals consisting of: (a) H, (b) C.sub.1-8 alkyl,
C.sub.1-8 alkenyl, C.sub.1-8 alkynyl, and (c) a substituted analog
of a radical of group (b), said substituted analog containing one
or more substituents selected from the group consisting of
hydroxyl, halogen, C.sub.1-6 alkyl, C.sub.3-8 cycloalkyl, C.sub.3-8
heterocycloalkyl, alkyloxy, amino, alkylamino, carboxyl, nitro,
sulfonylamide, alkylsulfonyl, amide, dioxoisoindole, trihaloalkyl,
aryl, and heteroaryl.
25. A compound of claim 1 wherein: B is NH; and R.sub.4 is selected
from the group consisting of: (a) C.sub.1-8 alkyl, C.sub.1-8
alkenyl, C.sub.1-8 alkynyl, aryl, and a heteroaryl containing one
or more heteroatoms selected from N, S and O, and (b) a substituted
radical of group (a) containing one or more substituents selected
from the group consisting of hydroxyl, halogen, C.sub.1-6 alkyl,
C.sub.3-8 cycloalkyl, C.sub.3-8 heterocycloalkyl, alkyloxy, amino,
alkylamino, carboxyl, nitro, sulfonylamide, alkylsulfonyl, amide,
dioxoisoindole, trihaloalkyl, and aryl.
26. A compound of claim 1 wherein: X is S. A is CH; B is CH.sub.2;
Z is CH; and W is CH.
27. A compound of claim 1 which is an acid selected from the group
consisting of hydrochloric, sulfuric, phosphoric,
p-toluenesulfonic, methanesulfonic, hydrobromic and
camphorsulfonic.
Description
[0001] This application claims priority under 35 U.S.C. 119(e) to
the Provisional application 60/726,814, filed on Oct. 13, 2005,
entitled "Novel Fab I Inhibitor And Process For Preparing Same,"
and to Provisional application 60/827,029 filed on Sep. 26, 2006,
both of which are hereby incorporated by reference.
FIELD OF THE INVENTION
[0002] The present invention relates to a novel compound for
inhibiting Fab I involved in bacterial fatty acid biosynthesis.
DESCRIPTION OF THE PRIOR ART
[0003] Fatty acid synthase (FAS) is involved in the overall
biosynthetic pathway of saturated fatty acids in all organisms, but
the structural organization of FAS varies considerably among them.
The distinctive characteristics of FAS of vertebrates and yeast are
that all enzymatic activities are encoded on one or two polypeptide
chains, and that the acyl carrier protein (ACP) exists in the form
of a complex. In contrast, in bacterial FAS, each of synthetic
steps is catalyzed by a distinct, mono-functional enzyme and the
ACP is a discrete protein. Therefore, it is possible to selectively
inhibit bacterial FAS by blocking one of the synthetic steps using
an inhibitory agent.
[0004] NADH-dependent enoyl-ACP reductase (Fab I) is involved in
the last step of the four reaction steps involved in each cycle of
bacterial fatty acid biosynthesis. (See Payne et al., Drug
Discovery Today 6, 2001, 537-544). The first step, the condensation
of malonyl-ACP with acetyl-CoA (Fab H), is catalyzed by
.beta.-ketoacyl-ACP synthase. The second step is ketoester
reduction by NADPH-dependent .beta.-ketoacyl-ACP reductase (Fab G).
Subsequent dehydration by .beta.-hydroxyacyl-ACP dehydrase (Fab A
or Fab Z) leads to trans-2-enoyl-ACP. Finally, in the fourth step,
trans-2-enoyl-ACP is converted to acyl-ACP having two additional
carbon atoms by Fab I. Such a cycle is repeated, eventually leading
to palmitoyl-ACP (16C), whereupon the cycle is stopped due to
inhibition of Fab I by palmitoyl-ACP (see Heath et al., J. Biol.
Chem. 271, 1996, 1833-1836). Thus, Fab I is the biosynthetic enzyme
in the overall synthetic pathway of bacterial fatty acid
biosynthesis.
[0005] Recent studies have shown that Fab I is the target for a
broad spectrum antibacterial agent such as triclosan (see McMurry
et al., Nature, 1998, 394, 531-532) or diazaborine (see Baldock et
al., Science, 1996, 274, 2107-2110). Also, diazaborine has been
reported to function as an irreversible inhibitor of Fab I through
the formation of a covalent complex with Fab I (see Baldock et al.,
Biochem. Pham., 1998, 55, 1541-1549), while triclosan is a
reversible inhibitor of Fab I (see Ward et al., Biochem., 38,
12514-12525).
[0006] PCT Publication No. WO 2001/027103 discloses Fab I
inhibitors represented by the following formula or pharmaceutically
acceptable salts thereof: ##STR1## ##STR2##
[0007] B is H, C.sub.1-4 alkyl or C.sub.3-6 cycloalkyl;
##STR3##
[0008] D is H or C.sub.1-4 alkyl;
[0009] E is CH.sub.2 when the bond to which it is attached is a
double bond; or E is H or C.sub.1-4 alkyl when the bond to which it
is attached is a single bond,
[0010] in which A is H or C.sub.1-4 alkyl;
[0011] F is H or C.sub.1-4 alkyl;
[0012] G is H, C.sub.1-4 alkyl or C.sub.0-6 alkylaryl;
[0013] I is O or NR'.sub.2;
[0014] Q is H, C.sub.1-4 alkyl, N(R').sub.2, NHC(O)R',
NHCH.sub.2C(O)R' or NHC(O)CH.dbd.CHR';
[0015] X is each independently H, C.sub.1-4 alkyl, CH.sub.2OH, OR',
SR', CN, N(R').sub.2, CH.sub.2N(R').sub.2, NO.sub.2, CF.sub.3,
CO.sub.2R', CON(R').sub.2, COR', F, Cl, Br, I or
--S(O).sub.rCF.sub.3 (r is 0, 1 or 2);
[0016] W is S or O;
[0017] M is CH.sub.2 or O;
[0018] L is CH.sub.2 or C(O); and
[0019] R' is each independently H, C.sub.1-4 alkyl or C.sub.0-6
alkylaryl.
[0020] In addition, PCT Publication Nos. WO 2004/052890 and WO
2004/064837 and Canadian Patent No. 2,444,957 disclose a Fab I
inhibitor for bacterial treatment.
[0021] The present inventors have developed a novel Fab I inhibitor
which has broad antibacterial activity against Gram positive
bacteria including methicillin resistant Staphylococcos Aureus
(MRSA).
SUMMARY OF THE INVENTION
[0022] It is an object of the present invention to provide a novel
compound which efficiently inhibits Fab I and is useful for the
treatment of bacterial infections.
[0023] In accordance with one aspect of the present invention,
there is provided a compound of formula (I) or (II) or a
pharmaceutically acceptable analog thereof selected from the group
consisting of salt, acid, ester, amide, and nitrile: ##STR4##
wherein,
[0024] R.sub.1 is selected from the group of radicals consisting
of: [0025] (a) H, [0026] (b) C.sub.1-8 alkyl, C.sub.1-8 alkenyl,
C.sub.1-8 alkynyl, [0027] (c) aryl, C.sub.3-8 cycloalkyl, C.sub.3-8
cycloalkenyl, [0028] (d) an analog of a radical of group (c)
containing one or more heteroatoms selected from N, S or and O, and
[0029] (e) a substituted analog of a radical selected from the
group consisting of groups (b), (c), and (d), said substituted
analog containing one or more substituents selected from the group
consisting of: [0030] hydroxyl, halogen, C.sub.1-6 alkyl, C.sub.3-8
cycloalkyl, C.sub.3-8 heterocycloalkyl, alkyloxy, amino,
alkylamino, carboxyl, nitro, sulfonylamide, alkylsulfonyl, amide,
dioxoisoindole, trihaloalkyl, aryl, heteroaryl, substituted aryl,
and substituted heteroaryl, [0031] wherein said substituted aryl
and substituted heteroaryl contain one or more substituents
selected from the group consisting of C.sub.1-6 alkyl, C.sub.3-8
cycloalkyl, C.sub.3-8 heterocycloalkyl, alkyloxy, amino,
alkylamino, carboxyl, nitro, sulfonylamide, alkylsulfonyl, amide,
dioxoisoindole, trihaloalkyl, aryl;
[0032] A is selected from the group consisting of C--R.sub.2 and
N;
[0033] R.sub.2 is selected from the group consisting of H,
C.sub.1-5 alkyl, benzyl, and substituted C.sub.1-5 alkyl containing
one or more substituents selected from the group consisting of
methyl, ethyl, hydroxyl, hydroxylmethyl and hydroxylethyl;
[0034] B is selected from the group consisting of carbonyl,
CH.sub.2 and NH;
[0035] R.sub.4 is selected from the group of radicals consisting
of: [0036] (a) C.sub.1-8 alkyl, C.sub.1-8 alkenyl, C.sub.1-8
alkynyl, [0037] (b) aryl, C.sub.3-8 cycloalkyl, C.sub.3-8
cycloalkenyl, [0038] (c) an analog of a radical of group (b)
containing one or more heteroatoms selected from N, S and O, and
[0039] (d) a substituted analog of a radical selected from the
group consisting of groups (a), (b), and (c), said substituted
analog containing one or more substituents selected from the group
consisting of: [0040] hydroxyl, halogen, C.sub.1-6 alkyl, C.sub.3-8
cycloalkyl, C.sub.3-8 heterocycloalkyl, alkyloxy, amino,
alkylamino, carboxyl, nitro, sulfonylamide, alkylsulfonyl, amide,
dioxoisoindole, trihaloalkyl, aryl, heteroaryl, substituted aryl,
and substituted heteroaryl, [0041] wherein said substituted aryl
and substituted heteroaryl contain one or more substituents
selected from the group consisting of: C.sub.1-6 alkyl, C.sub.3-8
cycloalkyl, C.sub.3-8 heterocycloalkyl, alkyloxy, amino,
alkylamino, carboxyl, nitro, sulfonylamide, alkylsulfonyl, amide,
dioxoisoindole, trihaloalkyl, and aryl;
[0042] W is selected from the group consisting of C--R.sub.6 and
N;
[0043] Z is selected from the group consisting of C--R.sub.5 and
N;
[0044] R.sub.5 and R.sub.6 are each independently selected from the
group consisting of H, halogen, C.sub.1-5 alkyl, and substituted
C.sub.1-5 alkyl containing one or more substituents selected from
the group consisting of methyl, ethyl, hydroxyl, hydroxylmethyl and
hydroxylethyl; and
[0045] X is selected from C, N, O and S.
DETAILED DESCRIPTION OF THE INVENTION
[0046] In accordance with one aspect of the present invention,
there is provided a novel compound of formula (I) or (II), or a
pharmaceutically acceptable salt thereof.
[0047] The term "heteroaryl" as used herein means an aryl group
containing one or more heteroatoms selected from N, S or O in the
ring structure. Exemplary heteroaryls include those derived from
pyrrole, pyrazole, imidazole, 1,2,3-triazole, 1,2,4-triazole,
furan, isoxazole, oxazole, thiophene, isothiazole, thiazolidine,
thiazole, 1,2,5-oxadiazole, 1,2,3-oxadiazole, 1,2,5-thiodiazole,
1,2,3-thiodiazole, 1,3,4-oxadiazole, 1,3,4-thiodiazole, pyridine,
pyrimidine, tetrazole and triazine.
[0048] The term "bacteria-related diseases" as used herein means
illnesses or conditions which are caused by bacterial infection and
may be alleviated or relieved by a Fab I inhibitor treatment, and
may include but are not limited to urinary tract, respiratory or
skin tissue infections, sepsis, etc.
[0049] It is to be understood that the inventive compound may
contain asymmetric centers of R or S configuration and thus the
present invention includes geometrical isomers, stereoisomers and
racemic mixtures of the compound of formula (I) or (II).
[0050] The pharmaceutically acceptable salt of the inventive
compound which may be a non-toxic addition salt may be prepared by
using an acid or base. Exemplary acids which may be used in the
present invention include such inorganic acids as hydrochloric,
hydrobromic, phosphoric and sulfuric acid; and an organic acid such
as an organic carboxylic acid, e.g., acetic, trifluoroacetic,
citric, formic, maleic, oxalic, succinic, benzoic, tartaric,
fumaric, mandelic, ascorbic and malic acid, methanesulfonic acid
and p-toluenesulfonic acid. Exemplary bases which may be used in
the present invention include such inorganic bases as an alkali
metal hydroxide (e.g., sodium hydroxide and potassium hydroxide),
an alkali metal bicarbonate (e.g., sodium bicarbonate and potassium
bicarbonate), an alkali metal carbonate (e.g., sodium carbonate,
potassium carbonate and calcium carbonate) and an organic base such
as amines.
[0051] The inventive compound may also be used in the form of a
pharmaceutically acceptable derivative or prodrug which has a
suitable ester or amide group. Preferable examples of the ester
which can be hydrolyzed chemically or biochemically in the living
body include indanyl, phthalidyl, pivaloyloxymethyl,
glycyloxymethyl, phenylglycyloxymethyl, and
5-methyl-2-oxo-1,3-dioxorene-4-ylmethyl esters.
[0052] The preferred compounds of the present invention are as
follows: [0053] 4-benzyloxy-1-(2-chloro-benzyl)-1H-pyridin-2-one;
[0054] 4-benzyloxy-1-(4-chloro-benzyl)-1H-pyridin-2-one; [0055]
4-benzyloxy-1-(4-nitro-benzyl)-1H-pyridin-2-one; [0056]
4-benzyloxy-1-(2,5-dichloro-benzyl)-1H-pyridin-2-one; [0057]
4-benzyloxy-1-(2,4-dichloro-benzyl)-1H-pyridin-2-one; [0058]
4-benzyloxy-2-(4-methoxy-benzyloxy)-pyridine; [0059]
4-benzyloxy-1-(4-methoxy-benzyl)-1H-pyridin-2-one; [0060]
4-benzyloxy-2-(4-methyl-benzyloxy)-pyridine; [0061]
4-benzyloxy-1-(4-methyl-benzyl)-1H-pyridin-2-one; [0062]
4-benzyloxy-1-(6-chloro-pyridin-3-ylmethyl)-1H-pyridin-2-one;
[0063] 4-benzyloxy-1-(3-chloro-benzyl)-1H-pyridin-2-one; [0064]
1-benzyl-4-benzyloxy-1H-pyridin-2-one; [0065]
1-(4-amino-benzyl)-4-benzyloxy-1H-pyridin-2-one; [0066]
1-(2,4-dichloro-benzyl)-4-hydroxy-1H-pyridin-2-one; [0067]
3-benzyl-1-(2,4-dichloro-benzyl)-4-hydroxy-1H-pyridin-2-one; [0068]
4-(biphenyl-4-ylmethoxy)-1-(2,4-dichloro-benzyl)-1H-pyridin-2-one;
[0069]
1-(2,4-dichloro-benzyl)-4-(2,4-dichloro-benzyloxy)-1H-pyridin-2-o-
ne; [0070]
4-(2-chloro-benzyloxy)-1-(2,4-dichloro-benzyl)-1H-pyridin-2-one;
[0071] 1-(2,4-dichloro-benzyl)-4-methoxy-1H-pyridin-2-one; [0072]
1-(2,4-dichloro-benzyl)-4-isopropoxy-1H-pyridin-2-one; [0073]
4-cyclohexylmethoxy-1-(2,4-dichloro-benzyl)-1H-pyridin-2-one;
[0074] 1-(2,4-dichloro-benzyl)-4-propoxy-1H-pyridin-2-one; [0075]
1-(2,4-dichloro-benzyl)-4-isobutoxy-1H-pyridin-2-one; [0076]
4-butoxy-1-(2,4-dichloro-benzyl)-1H-pyridin-2-one; [0077]
1-(2,4-dichloro-benzyl)-4-octyloxy-1H-pyridin-2-one; [0078]
1-(2,4-dichloro-benzyl)-4-(4-methyl-pentoxy)-1H-pyridin-2-one;
[0079] 4-(but-3-enyloxy)-1-(2,4-dichloro-benzyl)-1H-pyridin-2-one;
[0080] 1-(2,4-dichloro-benzyl)-4-pentyloxy-1H-pyridin-2-one; [0081]
[1-(2,4-dichloro-benzyl)-2-oxo-1,2-dihydro-pyridin-4-yloxy]-acetic
acid ethylester; [0082]
1-(2,4-dichloro-benzyl)-4-(3-methyl-butoxy)-1H-pyridin-2-one;
[0083] 1-benzyl-4-pentyloxy-1H-pyridin-2-one; [0084]
1-(2-chloro-benzyl)-4-pentyloxy-1H-pyridin-2-one; [0085]
4-pentyloxy-1-propyl-1H-pyridin-2-one; [0086]
1-butyl-4-pentyloxy-1H-pyridin-2-one; [0087]
1-isobutyl-4-pentyloxy-1H-pyridin-2-one; [0088]
1-(3-methyl-butyl)-4-pentyloxy-1H-pyridin-2-one; [0089]
1-(2,4-dichloro-benzyl)-4-hexyloxy-1H-pyridin-2-one; [0090]
1-(2,4-dichloro-benzyl)-4-heptyloxy-1H-pyridin-2-one; [0091]
1-(4-chloro-benzyl)-4-pentyloxy-1H-pyridin-2-one; [0092]
4-aryloxy-1-(2,4-dichloro-benzyl)-1H-pyridin-2-one; [0093]
1-(2,4-dichloro-benzyl)-4-(3-methoxy-propoxy)-1H-pyridin-2-one;
[0094]
1-(2,4-dichloro-benzyl)-4-(3-ethylamino-propoxy)-1H-pyridin-2-one;
[0095]
1-(2,4-dichloro-benzyl)-4-(2-ethoxy-ethoxy)-1H-pyridin-2-one;
[0096] 1-(3-methyl-but-2-enyl)-4-pentyloxy-1H-pyridin-2-one; [0097]
4-pentyloxy-1-thiazol-4-ylmethyl-1H-pyridin-2-one; [0098]
4-pentyloxy-1-pyridin-3-ylmethyl-1H-pyridin-2-one; [0099]
1-(2,4-dichloro-benzyl)-4-(4-methyl-pent-3-enyloxy)-1H-pyridin-2-one;
[0100]
1-(2,4-dichloro-benzyl)-4-(3-methoxy-propoxy)-1H-pyridin-2-one;
[0101] 1-(2,4-dichloro-benzyl)-4-phenetyloxy-1H-pyridin-2-one;
[0102] 1-(2-methyl-benzyl)-4-pentyloxy-1H-pyridin-2-one; [0103]
4-pentyl-1-phenetyl-1H-pyridin-2-one; [0104]
1-(2,4-dichloro-5-fluoro-benzyl)-4-pentyloxy-1H-pyridin-2-one;
[0105] 1-(3,4-dichloro-benzyl)-4-pentyloxy-1H-pyridin-2-one; [0106]
1-(3,4-difluoro-benzyl)-4-pentyloxy-1H-pyridin-2-one; [0107]
4-(4-benzyloxy-butoxy)-1-(2,4-dichloro-benzyl)-1H-pyridin-2-one;
[0108]
1-(2,4-dichloro-benzyl)-4-(4-hydroxy-butoxy)-1H-pyridin-2-one;
[0109]
4-(5-benzyloxy-pentyloxy)-1-(2,4-dichloro-benzyl)-1H-pyridin-2-one;
[0110]
1-(2,4-dichloro-benzyl)-4-(5-hydroxy-pentyloxy)-1H-pyridin-2-one;
[0111]
1-(6-chloro-benzo[1,3]dioxol-5-ylmethyl)-4-pentyloxy-1H-pyridin--
2-one; [0112]
1-(2,4-dichloro-benzyl)-4-(2-methyl-benzyloxy)-1H-pyridin-2-one;
[0113]
1-(2,4-dichloro-benzyl)-4-(4-methyl-benzyloxy)-1H-pyridin-2-one;
[0114] 1-(2-nitro-benzyl)-4-pentyloxy-1H-pyridin-2-one; [0115]
1-(2-amino-benzyl)-4-pentyloxy-1H-pyridin-2-one; [0116]
N-[2-(2-oxo-4-pentyloxy-2H-pyridin-1-ylmethyl)-phenyl]-acetamide;
[0117] 4-pentyloxy-1-(2-trifluoromethyl-benzyl)-1H-pyridin-2-one;
[0118]
N-[4-(4-benzyloxy-2-oxo-2H-pyridin-1-ylmethyl)-phenyl]acetamide;
[0119]
1-(2,4-dichloro-benzyl)-4-(naphthalen-2-ylmethoxy)-1H-pyridin-2-one;
[0120] 1-naphthalen-2-ylmethyl-4-pentyloxy-1H-pyridin-2-one; [0121]
4-benzyloxy-1-(6-chloro-benzo[1,3]dioxol-5-ylmethyl)-1H-pyridin-2-one;
[0122]
1-(6-chloro-benzo[1,3]dioxol-5-ylmethyl)-4-(3-methyl-butoxy)-1H-p-
yridin-2-one; [0123]
1-(2-methyl-benzyl)-4-(3-methyl-butoxy)-1H-pyridin-2-one; [0124]
4-(3-methyl-butoxy)-1-(2-nitro-benzyl)-1H-pyridin-2-one; [0125]
1-(2,4-dichloro-benzyl)-4-pentylamino-1H-pyridin-2-one; [0126]
1-(2,3-dichloro-benzyl)-4-pentyloxy-1H-pyridin-2-one; [0127]
1-(2-methoxy-benzyl)-4-pentyloxy-1H-pyridin-2-one; [0128]
1-(2,3-dimethoxy-benzyl)-4-pentyloxy-1H-pyridin-2-one; [0129]
4-(5-benzyloxy-pentyloxy)-1-(6-chloro-benzo[1,3]dioxol-5-ylmethyl)-1H-pyr-
idin-2-one; [0130]
1-(2-chloro-benzyl)-4-(3-methyl-butoxy)-1H-pyridin-2-one; [0131]
1-(3,4-dichloro-benzyl)-4-(3-methyl-butoxy)-1H-pyridin-2-one;
[0132]
1-(2,4-dichloro-5-fluoro-benzyl)-4-(3-methyl-butoxy)-1H-pyridin-2-one;
[0133] 1-benzyl-4-(3-methyl-butoxy)-1H-pyridin-2-one; [0134]
1-(4-chloro-benzyl)-4-(3-methyl-butoxy)-1H-pyridin-2-one; [0135]
1-(2,4-dichloro-benzyl)-4-pentyloxy-1H-pyrimidin-2-one; [0136]
1-(2,4-dichloro-benzyl)-4-(4-methyl-pentyloxy)-1H-pyrimidin-2-one;
[0137] 1-(2,4-dichloro-benzyl)-4-phenoxy-1H-pyrimidin-2-one; [0138]
4-(butyl-methyl-amino)-1-(2,4-dichloro-benzyl)-1H-pyrimidin-2-one;
[0139]
1-(2,4-dichloro-benzyl)-4-(2-diethylamino-ethoxy)-1H-pyrimidin-2--
one; [0140] 4-butoxy-1-(2,4-dichloro-benzyl)-1H-pyrimidin-2-one;
[0141] 1-(2,6-dichloro-benzyl)-4-pentyloxy-1H-pyridin-2-one; [0142]
1-(2-chloro-6-fluoro-benzyl)-4-pentyloxy-1H-pyridin-2-one; [0143]
1-(2-methyl-3-nitro-benzyl)-4-pentyloxy-1H-pyridin-2-one; [0144]
1-(3-amino-2-methyl-benzyl)-4-pentyloxy-1H-pyridin-2-one; [0145]
1-(4-methoxy-3,5-dimethyl-pyridin-2-ylmethyl)-4-pentyloxy-1H-pyridin-2-on-
e; [0146]
1-(6-chloro-benzo[1,3]dioxol-5-ylmethyl)-4-(5-hydroxy-pentyloxy)-1H-pyrid-
in-2-one; [0147]
1-(2-methoxy-5-nitro-benzyl)-4-pentyloxy-1H-pyridin-2-one; [0148]
1-(5-amino-2-methoxy-benzyl)-4-pentyloxy-1H-pyridin-2-one; [0149]
1-(2-ethyl-benzyl)-4-pentyloxy-1H-pyridin-2-one; [0150]
1-(2-chloro-5-nitro-benzyl)-4-pentyloxy-1H-pyridin-2-one; [0151]
1-(5-amino-2-chloro-benzyl)-4-pentyloxy-1H-pyridin-2-one; [0152]
1-(4-methoxy-2,3-dimethyl-benzyl)-4-pentyloxy-1H-pyridin-2-one;
[0153]
1-(2-methyl-pyridin-3-ylmethyl)-4-pentyloxy-1H-pyridin-2-one;
[0154]
N-[4-chloro-3-(2-oxo-4-pentyloxy-2H-pyridin-1-ylmethyl)-phenyl]-acetamide-
; [0155]
1-(2,4-dichloro-benzyl)-4-(3-dimethylamino-propoxy)-1H-pyridin--
2-one; [0156]
1-(2,4-dichloro-benzyl)-4-(4-dimethylamino-butoxy)-1H-pyridin-2-one;
[0157]
1-(2,4-dichloro-benzyl)-4-(6-dimethylamino-hexyloxy)-1H-pyrimidin-
-2-one; [0158]
1-(2,4-dimethyl-benzyl)-4-pentyloxy-1H-pyridin-2-one; [0159]
1-(2-chloro-5-trifluoromethyl-benzyl)-4-pentyloxy-1H-pyridin-2-on-
e; [0160] 1-(2-hydroxy-benzyl)-4-pentyloxy-1H-pyridin-2-one; [0161]
4-(3-cyclo-propoxy)-1-(2,4-dichloro-benzyl)-1H-pyrimidin-2-one;
[0162]
1-(2,4-dichloro-benzyl)-4-(3-methyl-pentyloxy)-1H-pyrimidin-2-one;
[0163] 1-(2,4-dichloro-benzyl)-4-hex-4-enyloxy-1H-pyrimidin-2-one;
[0164]
4-(2-cyclopropyl-ethoxy)-1-(2,4-dichloro-benzyl)-1H-pyrimidin-2-o-
ne; [0165]
1-(2,4-dichloro-benzyl)-4-(3-methyl-pentyloxy)-1H-pyridin-2-one;
[0166]
1-(2,4-dichloro-benzyl)-4-(5-morpholin-4-yl-pentyloxy)-1H-pyridin-2-one;
[0167] 1-(2-chloro-5-methoxy-benzyl)-4-pentyloxy-1H-pyridin-2-one;
[0168] 1-(2-chloro-5-ethoxy-benzyl)-4-pentyloxy-1H-pyridin-2-one;
[0169] 1-(2-chloro-5-propoxy-benzyl)-4-pentyloxy-1H-pyridin-2-one;
[0170]
1-[2-chloro-5-(2-hydroxy-ethoxy)-benzyl]-4-pentyloxy-1H-pyridin-2-
-one; [0171]
[4-chloro-3-(2-oxo-4-pentyloxy-2H-pyridin-1-ylmethyl)-oxy]-acetonitrile;
[0172]
1-[5-(2-amino-ethoxy)-2-chloro-benzyl]-4-pentyloxy-1H-pyridin-2-o-
ne; [0173]
N-[2-methyl-3-(2-oxo-4-pentyloxy-2H-pyridin-1-ylmethyl)-phenyl]-acetamide-
; [0174]
1-(2-methyl-3-methylamino-benzyl)-4-phenyloxy-1H-pyridin-2-one;
[0175]
1-(3-dimethylamino-2-methyl-benzyl)-4-phenyloxy-1H-pyridin-2-one- ;
[0176]
1-(3-ethylamino-2-methyl-benzyl)-4-pentyloxy-1H-pyridin-2-one;
[0177]
1-(3-diethylamino-2-methyl-benzyl)-4-pentyloxy-1H-pyridin-2-one;
[0178]
1-(2-methyl-3-propylamino-benzyl)-4-pentyloxy-1H-pyridin-2-one;
[0179]
1-(3-dipropylamino-2-methyl-benzyl)-4-pentyloxy-1H-pyridin-2-one;
[0180]
1-[3-(2-hydroxy-ethylamino)-2-methyl-benzyl]-4-pentyloxy-1H-pyri-
din-2-one; [0181]
1-(2-chloro-5-methoxy-4-nitro-benzyl)-4-pentyloxy-1H-pyridin-2-one;
[0182]
1-(4-amino-2-chloro-5-methoxy-benzyl)-4-pentyloxy-1H-pyridin-2-on-
e; [0183]
N-[5-chloro-2-methoxy-4-(2-oxo-4-pentyloxy-2H-pyridin-1-ylmethyl)-phenyl]-
-acetamide; [0184]
1-(2-chloro-5-methoxy-4-methylamino-benzyl)-4-pentyloxy-1H-pyridin-2-one;
[0185]
1-(2-chloro-4-dimethylamino-5-methoxy-benzyl)-4-pentyloxy-1H-pyr-
idin-2-one; [0186]
1-(2-chloro-4-ethylamino-5-methoxy-benzyl)-4-pentyloxy-1H-pyridin-2-one;
[0187]
1-(2-chloro-5-methoxy-4-propylamino-benzyl)-4-pentyloxy-1H-pyridi-
n-2-one; [0188]
1-[2-chloro-4-(2-hydroxy-ethylamino)-5-methoxy-benzyl]-4-pentyloxy-1H-pyr-
idin-2-one; [0189]
1-(4-amino-6-chloro-3-methoxy-2-nitro-benzyl)-4-pentyloxy-1H-pyridin-2-on-
e; [0190]
1-(2,4-diamino-6-chloro-3-methoxy-benzyl)-4-pentyloxy-1H-pyridin-2-one;
[0191]
1-(2,5-dichloro-6-methoxy-pyrimidin-4-ylmethyl)-4-pentyloxy-1H-py-
ridin-2-one; [0192]
1-(2,4-dichloro-benzenesulfonyl)-4-pentyloxy-1H-pyridin-2-one;
[0193] 1-(4-methanesulfonyl-benzyl)-4-pentyloxy-1H-pyridin-2-one;
[0194]
1-(4-amino-2-chloro-5-hydroxy-benzyl)-4-pentyloxy-1H-pyridin-2-one;
[0195] 4-(4-bromo-butoxy)-1-(2,4-dichloro-benzyl)-1H-pyridin-2-one;
[0196]
4-[1-(2,4-dichloro-benzyl)-2-oxo-1,2-dihydro-pyridin-4-yloxy]-but-
ylammonium; [0197]
1-(5-chloro-2,6-dimethoxy-pyrimidin-4-ylmethyl)-4-pentyloxy-1H-pyridin-2--
one; [0198]
1-(2-amino-5-chloro-6-methoxy-pyrimidin-4-ylmethyl)-4-pentyloxy-1H-pyridi-
n-2-one; [0199]
1-(6-amino-2,5-dichloro-pyrimidin-4-ylmethyl)-4-pentyloxy-1H-pyridin-2-on-
e; [0200]
5-chloro-6-(2-oxo-4-pentyloxy-2H-pyridin-1-ylmethyl)-3H-benzoxazol-2-one;
[0201] 1-(2-chloro-4-hydroxy-benzyl)-4-pentyloxy-1H-pyridin-2-one;
[0202]
1-(2-chloro-4-isopropoxy-benzyl)-4-pentyloxy-1H-pyridin-2-one;
[0203]
2-[3-(2-oxo-4-pentyloxy-2H-pyridin-1-yl)-propyl]-isoindole-1,3-di-
one; [0204] 1-(3-amino-propyl)-4-pentyloxy-1H-pyridin-2-one; [0205]
N-[3-(2-oxo-4-pentyloxy-2H-pyridin-1-yl)-propyl]-acetamide; [0206]
1-(3-dimethylamino-propyl)-4-pentyloxy-1H-pyridin-2-one; [0207]
1-(2,4-dichloro-benzyl)-6-methyl-4-pentyloxy-1H-pyridin-2-one;
[0208]
1-(2,4-dichloro-benzyl)-6-methyl-3-pentyl-4-pentyloxy-1H-pyridin-2-one;
[0209] 1-(2-amino-ethyl)-4-pentyloxy-1H-pyridin-2-one; [0210]
N-[2-(2-oxo-4-pentyloxy-2H-pyridin-1-yl)-ethyl]-acetamide; [0211]
N-[1,1-dimethyl-2-(2-oxo-4-pentyloxy-2H-pyridin-1-yl)-ethyl]-methanesulfo-
namide; [0212]
N-[1-(2-oxo-4-pentyloxy-2H-pyridin-1-ylmethyl)-propyl]-methanesulfonamide-
; [0213]
1-(7-nitro-benzo[1,3]dioxol-5-ylmethyl)-4-pentyloxy-1H-pyridin--
2-one; [0214]
1-(2-chloro-3-nitro-benzyl)-4-pentyloxy-1H-pyridin-2-one; [0215]
1-(3-amino-2-chloro-benzyl)-4-pentyloxy-1H-pyridin-2-one; [0216]
N-[2-chloro-3-(2-oxo-4-pentyloxy-2H-pyridin-1-ylmethyl)-phenyl]-acetamid-
e; [0217]
N-[2-chloro-3-(2-oxo-4-pentyloxy-2H-pyridin-1-ylmethyl)-phenyl]-methanesu-
lfonamide; [0218]
N,N'-[2-chloro-3-(2-oxo-4-pentyloxy-2H-pyridin-1-ylmethyl)-phenyl]dimetha-
nesulfonamide; [0219]
1-[2-chloro-3-(2-hydroxy-ethylamino)-benzyl]-4-pentyloxy-1H-pyridin-2-one-
; [0220]
4-chloro-2-(2-chloro-benzyl)-5-pentyloxy-2H-pyridazin-3-one; [0221]
2-(2-chloro-benzyl)-5-pentyloxy-2H-pyridazin-3-one; [0222]
1-(3-amino-2,6-dichloro-benzyl)-4-pentyloxy-1H-pyridin-2-one;
[0223]
1-(3-benzyloxy-2-chloro-4-methoxy-benzyl)-4-pentyloxy-1H-pyridin-2-one;
[0224]
1-(2-chloro-3,4-dimethoxy-benzyl)-4-pentyloxy-1H-pyridin-2-one;
[0225]
1-(2-chloro-3-hydroxy-4-methoxy-benzyl)-4-pentyloxy-1H-pyridin-2--
one; [0226]
1-[2-chloro-4-methoxy-3-(2-methoxy-ethoxy)-benzyl]-4-pentyloxy-1H-pyridin-
-2-one; [0227]
1-[2-chloro-4-methoxy-3-(2-pyrrolidin-1-yl-ethoxy)-benzyl]-4-pentyloxy-1H-
-pyridin-2-one; [0228]
1-[2-chloro-3-(2-dimethylamino-ethoxy)-4-methoxy-benzyl]-4-pentyloxy-1H-p-
yridin-2-one; [0229]
2-{3-[2-chloro-6-methoxy-3-(2-oxo-4-pentyloxy-2H-pyridin-1-ylmethyl)-phen-
oxyl]-propyl}-isoindole-1,3-dione; [0230]
1-[3-(2-dimethylamino-ethoxy)-2-methyl-benzyl]-4-pentyloxy-1H-pyridin-2-o-
ne; [0231]
1-[2-chloro-3-(2-dimethylamino-ethylamino)-benzyl]-4-pentyloxy-1H-pyridin-
-2-one; [0232]
1-[2,6-dichloro-3-(2-hydroxy-ethylamino)-benzyl]-4-pentyloxy-1H-pyridin-2-
-one; [0233]
1-[2,6-dichloro-3-(2-dimethylamino-ethylamino)-benzyl]-4-pentyloxy-1H-pyr-
idin-2-one; [0234]
1-[2,6-dichloro-3-(3-hydroxy-propylamino)-benzyl]-4-pentyloxy-1H-pyridin--
2-one; [0235]
1-[2,6-dichloro-3-(3-dimethylamino-propylamino)-benzyl]-4-pentyloxy-1H-py-
ridin-2-one; [0236]
1-[3-(3-amino-propylamino)-2,6-dichloro-benzyl]-4-pentyloxy-1H-pyridin-2--
one; [0237]
1-(3-fluoro-2-methyl-benzyl)-4-pentyloxy-1H-pyridin-2-one; [0238]
1-(2-chloro-3-dimethylaminomethyl-4-fluoro-benzyl)-4-pentyloxy-1H-
-pyridin-2-one; [0239]
1-(2,6-dichloro-3-methylamino-benzyl)-4-pentyloxy-1H-pyridin-2-one;
[0240]
1-(2,6-dichloro-3-dimethylamino-benzyl)-4-pentyloxy-1H-pyridin-2--
one; [0241]
[2-chloro-3-(2-oxo-4-pentyloxy-2H-pyridin-1-ylmethyl)-phenylamino]-acetic
acid; [0242]
1-(6-chloro-benzo[1,3]dioxol-5-ylmethyl)-4-(pyridin-4-ylmethoxy)-1H-pyrid-
in-2-one; [0243]
1-(6-chloro-benzo[1,3]dioxol-5-ylmethyl)-4-(6-chloro-pyridin-3-ylmethoxy)-
-1H-pyridin-2-one; [0244]
1-(6-chloro-benzo[1,3]dioxol-5-ylmethyl)-4-(4-methoxy-3,5-dimethylpyridin-
-2-ylmethoxy)-1H-pyridin-2-one; [0245]
1-(6-chloro-benzo[1,3]dioxol-5-ylmethyl)-4-(2-methyl-pyridin-3-ylmethoxy)-
-1H-pyridin-2-one; [0246]
1-(6-chloro-benzo[1,3]dioxol-5-ylmethyl)-4-(thiazol-4-ylmethoxy)-1H-pyrid-
in-2-one; [0247]
1-(6-chloro-benzo[1,3]dioxol-5-ylmethyl)-4-(pyridin-2-ylmethoxy)-1H-pyrid-
in-2-one; [0248] pentanoic acid
1-(6-chloro-benzo[1,3]dioxol-5-ylmethyl)-2-oxo-1,2-dihydro-pyridin-4-yl
ester; [0249] hexanoic acid
1-(6-chloro-benzo[1,3]dioxol-5-ylmethyl)-2-oxo-1,2-dihydro-pyridin-4-yl
ester; [0250]
1-(2-chloro-3-trifluoromethyl-benzyl)-4-pentyloxy-1H-pyridin-2-one;
[0251] thiophene-2-carboxyl acid
1-(6-chloro-benzo[1,3]dioxol-5-ylmethyl)-2-oxo-1,2-dihydro-pyridin-4-yl
ester; [0252] toluene-4-sulfonic acid
1-(6-chloro-benzo[1,3]dioxol-5-ylmethyl)-2-oxo-1,2-dihydro-pyridin-4-yl
ester; [0253]
1-(6-chloro-benzo[1,3]dioxol-5-ylmethyl)-4-(4,4,5,5,5-pentafluoro-pentylo-
xy)-1H-pyridin-2-one; [0254]
1-(6-chloro-benzo[1,3]dioxol-5-ylmethyl)-4-(2-dimethylamino-ethoxy)-1H-py-
ridin-2-one;
[0255]
1-(2,4-dichloro-benzyl)-4-(5-fluoro-pentyloxy)-1H-pyridin-2-one;
[0256]
3-[1-(2,4-dichloro-benzyl)-2-oxo-1,2-dihydro-pyridin-4-yloxymethy-
l]-indole-1-carboxyl acid tetra-butyl ester; [0257]
1-(2,4-dichloro-benzyl)-4-(2-thiophen-2-yl-ethoxy)-1H-pyridin-2-one;
[0258]
1-(2,4-dichloro-benzyl)-4-(2-thiophen-3-yl-ethoxy)-1H-pyridin-2-o-
ne; [0259]
1-(2,4-dichloro-benzyl)-4-(2-pyrrol-1-yl-ethoxy)-1H-pyridin-2-one;
[0260]
1-(2,4-dichloro-benzyl)-4-(3-pyrrol-1-yl-propoxy)-1H-pyridin-2-on-
e; [0261]
1-(3-amino-2-methyl-benzyl)-4-(2-thiophen-2-yl-ethoxy)-1H-pyridin-2-one;
[0262]
1-(3-amino-2-methyl-benzyl)-4-(2-pyrrol-1-yl-ethoxy)-1H-pyridin-2-
-one; [0263]
1-(3-amino-2-methyl-benzyl)-4-[2-(4-methyl-thiazol-5-yl)-ethoxy]-1H-pyrid-
in-2-one; [0264]
1-(3-amino-2-methyl-benzyl)-4-(2-(5-bromothiophen-2-yl)-ethoxy)-1H-pyridi-
n-2-one; [0265]
1-(3-amino-2-methyl-benzyl)-4-(2-(5-fluorothiophen-2-yl)-ethoxy)-1H-pyrid-
in-2-one; [0266]
1-[3-(2-hydroxy-ethylamino)-2-methyl-benzyl]-4-(2-thiophen-2-yl-ethoxy)-1-
H-pyridin-2-one; [0267]
2-{2-methyl-3-[2-oxo-4-(2-thiophene-2-yl-ethoxy)-2H-pyridin-1-ylmethyl]-p-
henylamino}-acetamide; [0268]
1-[3-(cyclopropylmethyl-amino)-2-methyl-benzyl]-4-(2-thiophen-2-yl-ethoxy-
)-1H-pyridin-2-one; [0269]
N-{2-methyl-3-[2-oxo-4-(2-thiophen-2-yl-ethoxy)-2H-pyridin-1-ylmethyl]-ph-
enylamino}-acetonitrile; [0270]
N-(2-{2-methyl-3-[2-oxo-4-(2-thiophen-2-yl-ethoxy)-2H-pyridin-1-ylmethyl]-
-phenylamino}-ethyl)-acetamide; [0271]
1-[2-methyl-3-(2-pyrrol-1-yl-ethylamino)-benzyl]-4-(2-thiophen-2-yl-ethox-
y)-1H-pyridin-2-one; [0272]
1-[2-methyl-3-(2-oxo-2-pyrrolidin-1-yl-ethylamino)-benzyl]-4-(2-thiophen--
2-yl-ethoxy)-1H-pyridin-2-one; [0273]
1-[2-methyl-3-(2-oxo-2-piperidin-1-yl-ethylamino)-benzyl]-4-(2-thiophen-2-
-yl-ethoxy)-1H-pyridin-2-one; [0274]
N,N-dimethyl-2-{2-methyl-3-[2-oxo-4-(2-thiophen-2-yl-ethoxy)-2H-pyridin-1-
-ylmethyl]-phenylamino}-acetamide; [0275]
1-{2-methyl-3-[2-(4-methyl-piperazin-1-yl)-2-oxo-ethylamino]-benzyl}-4-(2-
-thiophen-2-yl-ethoxy)-1H-pyridin-2-one; [0276]
1-[2-methyl-3-(2-morpholin-4-yl-2-oxo-ethylamino)-benzyl]-4-(2-thiophen-2-
-yl-ethoxy)-1H-pyridin-2-one; [0277]
1-(3-amino-2-methyl-benzyl)-4-(2-furan-2-yl-ethoxy)-1H-pyridin-2-one;
[0278]
1-(3-amino-2-methyl-benzyl)-4-[2-(5-methyl-thiophen-2-yl)-ethoxy]-
-1H-pyridin-2-one; [0279]
1-(3-amino-2-methyl-benzyl)-4-[2-(5-chloro-thiophen-2-yl)-ethoxy]-1H-pyri-
din-2-one; [0280]
1-(2,4-dichloro-benzyl)-4-[2-(3-methyl-thiophen-2-yl)-ethoxy]-1H-pyridin--
2-one; [0281]
1-(3-amino-2-methyl-benzyl)-4-(2-benzo[b]thiophen-3-yl-ethoxy)-1H-pyridin-
-2-one; [0282]
1-(3-amino-2-methyl-benzyl)-4-[2-(5-chloro-3-methyl-benzo[b]thiophen-2-yl-
)-ethoxy]-1H-pyridin-2-one; [0283]
1-(3-amino-2-methyl-benzyl)-4-[2-(3-methyl-benzo[b]thiophen-2-yl)-ethoxy]-
-1H-pyridin-2-one; [0284]
1-(3-amino-2-methyl-benzyl)-4-[2-(5-methyl-furan-2-yl)-ethoxy]-1H-pyridin-
-2-one; [0285]
1-(3-amino-2-methyl-benzyl)-4-[2-(5-ethyl-furan-2-yl)-ethoxy]-1H-pyridin--
2-one; [0286]
5-[1-(3-amino-2-methyl-benzyl)-2-oxo-1,2-dihydro-pyridin-4-yloxymethyl]-f-
uran-2-carboxylic acid ethyl ester; [0287]
1-[3-(2-dimethylamino-ethylamino)-2-methyl-benzyl]-4-(2-thiophen-2-yl-eth-
oxy)-1H-pyridin-2-one; [0288]
1-(3-amino-2-methyl-benzyl)-4-[2-(5-methylsulfanyl-thiophen-2-yl)-ethoxy]-
-1H-pyridin-2-one; [0289]
1-(3-amino-2-methyl-benzyl)-4-(2-benzofuran-2-yl-ethoxy)-1H-pyridin-2-one-
; [0290]
1-(3-amino-2-methyl-benzyl)-4-[2-(3-methyl-isoxazol-5-yl)-ethox-
y]-1H-pyridin-2-one; [0291]
1-(3-amino-2-methyl-benzyl)-4-[2-(4,5-dimethyl-thiophen-2-yl)-ethoxy]-1H--
pyridin-2-one; [0292]
1-(3-amino-2-methyl-benzyl)-4-[2-(5-ethyl-thiophen-2-yl)-ethoxy]-1H-pyrid-
in-2-one; [0293]
1-(3-amino-2,6-dichloro-benzyl)-4-(2-thiophen-2-yl-ethoxy)-1H-pyridin-2-o-
ne; [0294]
N-{2-methyl-3-[2-oxo-4-(2-thiophen-2-yl-ethoxy)-2H-pyridin-1-ylmethyl]-ph-
enyl}-acetamide; [0295]
1-[2-methyl-3-(2-piperidin-1-yl-ethylamino)-benzyl]-4-(2-thiophen-2-yl-et-
hoxy)-1H-pyridin-2-one; [0296]
1-[2-methyl-3-(2-morpholin-4-yl-ethylamino)-benzyl]-4-(2-thiophen-2-yl-et-
hoxy)-1H-pyridin-2-one; [0297]
N-{2-methyl-3-[2-oxo-4-(2-thiophen-2-yl-ethoxy)-2H-pyridin-1-ylmethyl]-ph-
enyl}-methanesulfonamide; [0298]
1-(3-amino-2-methyl-benzyl)-4-[2-(4-bromo-thiophen-2-yl)-ethoxy]-1H-pyrid-
in-2-one; [0299]
1-(6-chloro-benzo[1,3]dioxol-5-ylmethyl)-4-(2-pyrrol-1-yl-ethoxy)-1H-pyri-
din-2-one; [0300]
1-(6-chloro-benzo[1,3]dioxol-5-ylmethyl)-4-(2-thiophen-2-yl-ethoxy)-1H-py-
ridin-2-one; [0301]
1-[2-methyl-3-(2-pyrrolidin-1-yl-ethylamino)-benzyl]-4-(2-thiophen-2-yl-e-
thoxy)-1H-pyridin-2-one; [0302]
N-(2-{2-methyl-3-[2-oxo-4-(2-thiophen-2-yl-ethoxy)-2H-pyridin-1-ylmethyl]-
-phenylamino}-ethyl)-acetamide; [0303]
1-{2-methyl-3-[(pyridin-3-ylmethyl)-amino]-benzyl}-4-(2-thiophen-2-yl-eth-
oxy)-1H-pyridin-2-one; [0304]
2-methyl-3-[2-oxo-4-(2-thiophen-2-yl-ethoxy)-2H-pyridin-1-ylmethyl]-pheny-
l ester; [0305]
1-{2-methyl-3-[(pyridin-4-ylmethyl)-amino]-benzyl}-4-(2-thiophen-2-yl-eth-
oxy)-1H-pyridin-2-one; [0306]
1-{2-methyl-3-[(thiazol-4-ylmethyl)-amino]-benzyl}-4-(2-thiophen-2-yl-eth-
oxy)-1H-pyridin-2-one; [0307]
1-[3-(4-methoxy-benzyloxy)-2-methyl-benzyl]-4-(2-thiophen-2-yl-ethoxy)-1H-
-pyridin-2-one; [0308]
1-{3-[(3,5-dimethyl-isoxazol-4-ylmethyl)-amino]-2-methyl-benzyl}-4-(2-thi-
ophen-2-yl-ethoxy)-1H-pyridin-2-one; [0309]
1-(3-hydroxy-2-methyl-benzyl)-4-(2-thiophen-2-yl-ethoxy)-1H-pyridin-2-one-
; [0310]
1-{2-methyl-3-[(1-methyl-pyrrolidin-2-ylmethyl)-amino]-benzyl}--
4-(2-thiophen-2-yl-ethoxy)-1H-pyridin-2-one; [0311]
1-{2-methyl-3-[2-(1-methyl-pyrrolidin-2-yl)-ethylamino]-benzyl}-4-(2-thio-
phen-2-yl-ethoxy)-1H-pyridin-2-one; [0312]
(2-{2-methyl-3-[2-oxo-4-(2-thiophen-2-yl-ethoxy)-2H-pyridin-1-ylmethyl]-p-
henylamino}-ethyl)-phosphonic acid diethyl ester; [0313]
4-(isobutylthio)-1-(2-methyl-3-nitrobenzyl)pyridine-2(1H)-one;
[0314]
1-(3-amino-2-methylbenzyl)-4-(isobutylthio)pyridine-2(1H)-one;
[0315]
1-(3-amino-2-methylbenzyl)-4-(furan-2-ylmethylthio)pyridine-2(1H)-one;
[0316]
1-(3-amino-2-methylbenzyl)-4-(pentylthio)pyridine-2-(1H)-one;
[0317]
1-(3-amino-2-methylbenzyl)-4-(phenethylthio)pyridine-2(1H)-one;
[0318] 1-(3-amino-2-methylbenzyl)-4-(butylthio)pyridine-2(1H)-one;
[0319]
1-(3-amino-2-methylbenzyl)-4-(thiophen-2-ylmethylthio)pyridine-2(-
1H)-one; [0320]
1-(3-amino-2-methylbenzyl)-4-(pentylthio)pyridine-2(1H)-one; [0321]
1-(3-amino-2-methylbenzyl)-4-(propylthio)pyridine-2(1H)-one; [0322]
1-(3-amino-2-methylbenzyl)-4-(1-methylbutylthio)pyridine-2
(1H)-one; [0323]
N,N-dimethyl-3-(2-methyl-3-((2-oxo-4-(2-(thiophen-2-yl)ethoxy)pyr-
idin-1(2H)-yl)methyl)phenylamino)prop ane-1-sulfonamide; [0324]
1-(3-amino-2-methylbenzyl)-4-(2-(thiophene-2-yl)ethylamino)pyridine-2-(1H-
)-one.
[0325] The compound of formula (I) or (II) may be prepared by
simple alkylation or arylation using pyridazine derivative,
pyrimidinone derivative, triazinone derivative or pyridone
derivative.
[0326] A preferred example of the compound of formula (I) is a
pyridone compound which may be prepared as shown in Reaction Scheme
1 or 2. As used herein, NaH is sodium hydride, TsCl is
p-toluenesulfonyl chloride, Ac.sub.2O is acetic anhydride, BuOH is
butanol, t-BuOH is t-butanol, Pd/C is palladium on carbon, KOtBu is
potassium t-butoxide, and Zn is zinc dust. Reaction Scheme 1
##STR5## Reagents: (a) NaH, benzyloxypropyl bromide, DMF; (b) Pd/C,
H.sub.2, MeOH; (c) TsCl, TEA, DCM; (d) cyclopropylamine, MeOH
##STR6## Reagents: (a) NaH, 2-methyl-3-nitrobenzyl chloride, DMF;
(b) hydrazine, Zn, EtOH; (c) Acetic anhydride, TEA, DCM
[0327] The pyridone derivatives used as starting materials above
may be prepared as shown in Reaction Scheme 3 or 4, respectively.
##STR7## Reagents: (a) BnCl, NaH, DMF; (b) Pd/C, H.sub.2, MeOH
##STR8## Reagents: (a) BuOH, KOtBu t-BuOH; (b) Ac.sub.2O,
reflux
[0328] Another preferred example of the compound of formula (I) is
a pyridone compound being substituted with a methyl group, which
may be prepared as shown in Reaction Scheme 5. ##STR9## Reagents:
(a) NaH, pentyl bromide, DMF; (b) benzyl amine, EtOH, reflux
[0329] Still another preferred example of the compound of formula
is a pyridazine compound, which may be prepared as shown in
Reaction Scheme 6. ##STR10## Reagents: (a) NaH, pentanol, DMF; (b)
2,4-dichlorobenzyl chloride, NaH, DMF; (c) pd/C, H.sub.2, MeOH
[0330] Substituting 4-methylpentanol for pentanol in Reaction
Scheme 6 will produce 2,
(2,4-dichlorobenzyl)-5-4-methylpentyloxy)pyridazin-3(2H)-one:
##STR11## [0331]
(2,4-dichlorobenzyl)-5-4-methylpentyloxy)pyridazin-3(2H)-one
[0332] The compound of formula (I) or (II) effectively inhibits the
activity of Fab I. Accordingly, the present invention provides a
method for inhibiting the activity of Fab I, comprising bringing a
body fluid such as blood, urine and lymph into contact with the
compound of formula (I) or (II).
[0333] The present invention also provides a pharmaceutical
composition comprising the compound of formula (I) or (II) as an
active ingredient in an amount effective to treat or prevent
bacteria-related diseases.
[0334] The inventive pharmaceutical composition may comprise
pharmaceutically acceptable carriers, diluents, adjuvants or
vehicles. Exemplary carriers, diluents, adjuvants and vehicles
include, but are not limited to, ion exchangers, alumina, aluminum
stearate, lecithin, serum proteins such as human serum albumin,
buffer substances such as phosphates, glycine, sorbic acid,
potassium sorbate, partial glyceride mixtures of saturated
vegetable fatty acids, water, salts or electrolytes such as
protamine sulfate, disodium hydrogen phosphate, potassium hydrogen
phosphate, sodium chloride or zinc salts, colloidal silica,
magnesium trisilicate, polyvinyl pyrrolidone, cellulose-based
substances, polyethylene glycol, sodium carboxy methylcellulose,
polyacrylates, waxes, polyethylene-polyoxypropylene-block polymers,
polyethylene glycol, wool fat, parabens, chlorobutanol, phenol,
sorbic acid, aluminum monostearate, gelatin and the like. It may
also be desirable to include isotonic agents, for example sugars,
sodium chloride, and the like.
[0335] Various formulations of the present invention may be
prepared using surfactants such as TWEENs.TM. or SPANs.TM.,
emulsifying agents, extenders, etc., and may be administered
orally, sublingually, parenterally, by inhalation spray, topically,
rectally, nasally, buccally, vaginally or via an implanted
reservoir The term "parenteral" as used herein includes
subcutaneous, intravenous, intramuscular, intra-articular,
intra-synovial, intrasternal, intrathecal, intrahepatic,
intralesional and intracranial injection or infusion techniques.
Preferably, the composition is administered orally,
intraperitoneally, subcutaneously, intramuscularly or
intravenously.
[0336] Sterile injectable formulations may be in the form of
aqueous or oleaginous suspensions. These suspensions may be
formulated by a conventional method using suitable dispersing or
wetting agents and suspending agents such as water, ethanol,
polyols (propyleneglycol, polyethyleneglycol, glycerol, and the
like), suitable mixtures thereof, vegetable oils (such as olive
oil), and injectable organic esters such as ethyl oleate. Proper
fluidity can be maintained, for example, by the use of a coating
such as lecithin, by the maintenance of the required particle size
in the case of dispersions and by the use of surfactants.
[0337] Formulations suitable for oral administration may be in the
form of capsules, tablets, pills, powders, or granules. In such
solid dosage forms, the active compound can be admixed with at
least one inert carrier such as sodium citrate or dicalcium
phosphate; or with fillers, extenders, binders, humectants,
disintegrating agents such as calcium carbonate or certain complex
silicates, solution retarders such as paraffin, absorption
accelerators such as quaternary ammonium compounds, wetting agents
such as cetyl alcohol or glycerol monostearate, adsorbents, and
lubricants such as magnesium stearate, solid polyethylene glycols,
and the like, or mixtures thereof. In the form of capsules, the
active compound can be admixed with buffering agents, and can also
be admixed with excipients such as lactose or milk sugar as well as
high molecular weight polyethyleneglycols, and the like.
[0338] Formulations suitable for oral administration may
alternatively be in the form of aqueous suspensions, solutions,
syrups, etc. When aqueous suspensions are required for oral use,
the active ingredient is combined with emulsifying and suspending
agents. If desired, certain sweetening, flavoring or coloring
agents may also be added.
[0339] Formulations for oral administration can include a coating,
and can be formulated with certain agents so as to release the
active compound in a particular portion of the digestive tract.
[0340] Formulations for topical administration may be useful in
that the target of treatment includes areas or organs readily
accessible by topical application, e.g., the eye, the skin or the
lower intestinal tract. Topically-transdermal patches may also be
used for topical administration.
[0341] For topical application to the skin or the lower intestinal
tract, the compositions may be formulated in the form of ointments,
lotions, creams or sprays form containing the active component
suspended or dissolved in one or more suitable carriers. The
ointments may contain mineral oil, liquid petrolatum, white
petrolatum, propylene glycol, polyoxyethylene, polyoxypropylene,
emulsifying wax or water as suitable carriers. The lotions, creams
or sprays may contain mineral oil, sorbitan monostearate,
polysorbate 60, cetyl esters wax, cetearyl alcohol,
2-octyldodecanol, benzyl alcohol or water as suitable carriers.
[0342] For ophthalmic use, the compositions may be formulated as
micronized suspensions or solutions in isotonic, pH adjusted
sterile saline, either with or without a preservative such as
benzylalkonium chloride. Alternatively, the compositions may be
formulated in ophthalmic ointments such as petrolatum.
[0343] Formulations suitable for administration by nasal aerosol or
inhalation may be in the form of solutions in saline. The solutions
may contain benzyl alcohol or other suitable preservatives,
absorption promoters to enhance bioavailability, fluorocarbons,
and/or other conventional solubilizing or dispersing agents.
[0344] Formulations suitable for rectal or vaginal administration
can be prepared by mixing the compounds of the present invention
with suitable non-irritating excipients or carriers such as a
suppository wax, cocoa butter, or polyethyleneglycol which melt at
body temperature.
[0345] If necessary, the inventive compound may be used with other
antimicrobials such as penicillin or cephalosporin.
[0346] A single dose of the compound of formula (I) or (II) may
range from about 50 to 1,500 mg, although the dose may be varied
depending upon the age, body weight and symptoms of the patient. A
typical daily dose of the compound of formula (I) or (II) may range
from about 50 to 5,000 mg, or from about 150 to 3,000 mg for
adults, and can be from about 50 to 2000 mg, or from about 100 to
2000 mg, or from about 300 to 2500 mg, or from about 500 to 4000
mg, or from about 500 to 5000 mg.
[0347] Further, the present invention provides a method for
treating bacteria-related diseases, comprising administering an
effective amount of a compound of formula (I) or (II) to a patient
in need of such treatment. The patient to be treated by the above
method may include a human or non-human mammalian.
[0348] The present invention will be described in further detail
with reference to Examples. However, it should be understood that
the present invention is not restricted by the specific
Examples.
PREPARATION EXAMPLE 1
Synthesis of 4-pentyloxy-1H-pyridin-2-one
[0349] A solution of pentanol (2.7 g, 31 mmol) and tert-butoxide
(3.5 g, 31 mmol) in solvent of tert-butanol was stirred for 1 hr at
room temperature followed by addition of 4-nitropyridine-N-oxide (4
g, 28.6 mmol). After the reaction was done, the resulting solution
was worked up with ethyl acetate and water, separated and the
organic solvent was dried completely. After the addition of
toluene, the solvent was removed under a reduced pressure. Acetic
anhydride (40 ml) was added to the residual mixture and refluxed
for 3 hrs. Acetic anhydride was dried completely followed by adding
of MeOH (20 ml) and 3N NaOH (5 ml) and stirring 1 hr. MeOH was
dried adequately then the residual mixture was made neutral with 6N
HCl. The resulting solution was extracted with Ethyl acetate (80
ml) and subjected to silica gel column chromatography (ethyl
acetate/MeOH, 10:1) to obtain the titled compound (2.3 g, 56%).
[0350] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 0.93 (t 3H),
1.33-1.44 (m, 4H), 1.72-1.79 (m, 2H), 3.91 (t, 2H), 5.91-6.08 (m,
2H), 7.40 (d, 1H)
EXAMPLE 1
4-benzyloxy-1-(2-chloro-benzyl)-1H-pyridin-2-one
[0351] A solution of 4-benzyloxy-1H-pyridone (300 mg, 1.49 mmol)
and NaH (60 mg, 1.49 mmol) in solvent of DMF was stirred for 30 min
followed by adding 2-chlorobenzyl chloride (240 mg, 1.49 mmol)
further stirring for 30 min at room temperature. The resulting
solution was worked up with Water and dichloromethane and purified
by column chromatography (ethyl acetate/hexane, 1:1) to obtain the
titled compound (320 mg, 67%).
[0352] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 5.00 (s, 2H), 5.20
(s, 2H), 5.97 (dd, 1H), 6.04 (d, 1H), 7.17-7.39 (m, 10H)
EXAMPLES 2 TO 13
[0353] The procedure of Example 1 was repeated except the starting
material to obtain the titled compound.
EXAMPLE 2
4-benzyloxy-1-(4-chloro-benzyl)-1H-pyridin-2-one
[0354] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 4.96 (s, 2H), 5.01
(s, 2H), 5.93 (dd, 1H), 5.99 (d, 1H), 7.09 (d, 1H), 7.19 (d, 2H),
7.24 (d, 2H), 7.28-7.36 (m, 5H)
EXAMPLE 3
4-benzyloxy-1-(4-nitro-benzyl)-1H-pyridin-2-one
[0355] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 5.08 (s, 2H), 5.47
(s, 2H), 6.39-6.60 (m, 2H), 7.35-7.59 (m, 7H), 7.95 (d, 1H),
8.18-8.23 (m, 2H)
EXAMPLE 4
4-benzyloxy-1-(2,5-dichloro-benzyl)-1H-pyridin-2-one
[0356] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 4.98 (s, 2H), 5.12
(s, 2H), 5.96-6.03 (m, 2H), 7.14-7.39 (m, 9H)
EXAMPLE 5
4-benzyloxy-1-(2,4-dichloro-benzyl)-1H-pyridin-2-one
[0357] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 5.00 (s, 2H), 5.14
(s, 2H), 5.97-6.03 (m, 2H), 7.18-7.41 (m, 9H)
EXAMPLE 6
4-benzyloxy-2-(4-methoxy-benzyloxy)-pyridine
[0358] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 3.80 (s, 3H), 5.05
(s, 2H), 5.28 (s, 2H), 6.31 (d, 1H), 6.55 (dd, 1H), 6.90 (d, 1H),
7.29-7.40 (m, 7H), 7.99 (d, 1H)
EXAMPLE 7
4-benzyloxy-1-(4-methoxy-benzyl)-1H-pyridin-2-one
[0359] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 3.79 (s, 3H), 4.98
(s, 2H), 5.01 (s, 2H) 5.92 (dd, 1H), 6.01 (d, 1H), 6.86 (d, 2H),
7.11 (d, 1H), 7.22-7.26 (m, 3H), 7.34-7.38 (m, 4H)
EXAMPLE 8
4-benzyloxy-2-(4-methyl-benzyloxy)-pyridine
[0360] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 2.37 (s, 3H), 5.06
(s, 2H), 5.33 (s, 2H), 6.34 (d 1H), 6.56 (dd, 1H), 7.19 (d, 2H),
7.34-7.41 (m, 7H), 8.00 (d, 1H)
EXAMPLE 9
4-benzyloxy-1-(4-methyl-benzyl)-1H-pyridin-2-one
[0361] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 2.33 (s, 3H), 4.98
(s, 2H), 5.04 (s, 2H) 5.93 (dd, 1H), 6.02 (d, 1H), 7.10-7.19 (m,
5H), 7.34-7.38 (m, 5H)
EXAMPLE 10
4-benzyloxy-1-(6-chloro-pyridin-3-ylmethyl)-1H-pyridin-2-one
[0362] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 4.99 (s, 2H), 5.04
(s, 2H), 6.00-6.02 (m, 2H), 7.15-7.38 (m, 7H), 7.66 (dd, 1H),
8.34-8.37 (m, 1H)
EXAMPLE 11
4-benzyloxy-1-(3-chloro-benzyl)-1H-pyridin-2-one
[0363] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 4.96 (s, 2H), 5.01
(s, 2H), 5.94 (dd, 1H), 6.00 (d, 1H), 7.09-7.36 (m, 10H)
EXAMPLE 12
1-benzyl-4-benzyloxy-1H-pyridin-2-one
[0364] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 4.96 (s, 2H), 5.06
(s, 2H), 5.92 (dd, 1H), 6.01 (d, 1H), 7.10 (d, 1H), 7.24-7.36 (m,
10H)
EXAMPLE 13
1-(4-amino-benzyl)-4-benzyloxy-1H-pyridin-2-one
[0365] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 3.73 (br s, 2H),
4.95 (s, 2H), 4.97 (s, 2H), 5.90 (dd, 1H), 6.00 (d, 1H), 6.63 (d,
2H), 7.08-7.37 (m, 8H)
EXAMPLE 14
1-(2,4-dichloro-benzyl)-4-hydroxy-1H-pyridin-2-one
[0366] 4-benzyloxy-1-(2,4-dichloro-benzyl)-1H-pyridin-2-one
synthesized by the same method as Example 1 was hydrogenated with
Pd/C to obtain the titled compound.
[0367] .sup.1H NMR (CD.sub.3OD, 300 MHz) .delta. 5.17 (s, 2H), 5.86
(d, 1H), 6.10 (dd, 1H), 6.99 (d, 1H), 7.27-7.32 (m, 1H), 7.50-7.52
(m, 2H)
EXAMPLE 15
3-benzyl-1-(2,4-dichloro-benzyl)-4-hydroxy-1H-pyridin-2-one
[0368] 1-(2,4-dichloro-benzyl)-4-hydroxy-1H-pyridin-2-one
synthesized in Example 14 was dissolved in DMF followed by adding
NaH and benzyl bromide to obtain
4-benzyloxy-1-(2,4-dichloro-benzyl)-1H-pyridin-2-one and the titled
compound in the ratio of 1:1.
[0369] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 4.00 (s, 2H), 5.13
(s, 2H), 5.87 (d, 1H), 7.25-7.33 (m, 9H)
EXAMPLES 16 TO 225
[0370] The procedure of Example 1 was repeated except the starting
material to obtain the titled compound.
EXAMPLE 16
4-(biphenyl-4-ylmethoxy)-1-(2,4-dichloro-benzyl)-1H-pyridin-2-one
[0371] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 5.04 (s, 2H), 5.15
(s, 2H), 6.01 (dd, 1H), 6.06 (d, 1H), 7.22-7.63 (m, 13H)
EXAMPLE 17
1-(2,4-dichloro-benzyl)-4-(2,4-dichloro-benzyloxy)-1H-pyridin-2-one
[0372] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 5.06 (s, 2H), 5.15
(s, 2H), 5.99-6.01 (m, 2H), 7.15-7.44 (m, 7H)
EXAMPLE 18
4-(2-chloro-benzyloxy)-1-(2,4-dichloro-benzyl)-1H-pyridin-2-one
[0373] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 5.11 (s, 2H), 5.16
(s, 2H), 6.00-6.04 (m, 2H), 7.21-7.47 (m, 8H)
EXAMPLE 19
1-(2,4-dichloro-benzyl)-4-methoxy-1H-pyridin-2-one
[0374] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 3.78 (s, 3H), 5.14
(s, 2H), 5.91-5.94 (m, 2H), 7.16-7.22 (m, 3H), 7.41 (s, 1H)
EXAMPLE 20
1-(2,4-dichloro-benzyl)-4-isopropoxy-1H-pyridin-2-one
[0375] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 1.34 (d, 6H),
4.47-4.55 (m, 1H), 5.86-5.91 (m, 2H), 7.15-7.21 (m, 3H), 7.41 (s,
1H)
EXAMPLE 21
4-cyclohexylmethoxy-1-(2,4-dichloro-benzyl)-1H-pyridin-2-one
[0376] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 0.86-1.83 (m,
11H), 3.71 (d, 2H), 5.14 (s, 2H), 5.90-5.94 (m, 2H), 7.15-7.23 (m,
3H), 7.40 (s, 1H)
EXAMPLE 22
3-(2-chloro-benzyl)-4-hydroxy-1H-pyridin-2-one
[0377] .sup.1H NMR (CD.sub.3OD, 300 MHz) .delta. 3.82 (s, 2H), 6.12
(d, 1H), 7.06-7.28 (m, 5H)
EXAMPLE 23
1-(2,4-dichloro-benzyl)-4-propoxy-1H-pyridin-2-one
[0378] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 1.02 (t 3H),
1.74-1.85 (m, 2H), 3.88 (t, 2H), 5.14 (s, 2H), 5.91-5.94 (m, 2H),
7.15-7.24 (m, 3H), 7.40 (s, 1H)
EXAMPLE 24
1-(2,4-dichloro-benzyl)-4-isobutoxy-1H-pyridin-2-one
[0379] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 1.00 (d, 6H),
2.03-2.12 (m, 1H), 3.68 (d, 2H), 5.14 (s, 2H), 5.90-5.95 (m, 2H),
7.15-7.23 (m, 3H), 7.41 (s, 1H)
EXAMPLE 25
4-butoxy-1-(2,4-dichloro-benzyl)-1H-pyridin-2-one
[0380] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 0.97 (t, 3H),
1.40-1.52 (m, 2H), 1.71-1.80 (m, 2H), 3.92 (t, 2H), 5.14 (s, 2H),
5.90-5.92 (m, 2H), 7.15-7.23 (m, 3H), 7.41 (s, 1H)
EXAMPLE 26
1-(2,4-dichloro-benzyl)-4-octyloxy-1H-pyridin-2-one
[0381] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 0.84 (t 3H),
1.24-1.52 (m, 10H), 1.67-1.76 (m, 2H), 3.86 (t, 2H), 5.09 (s, 2H),
5.86-5.89 (m, 2H), 7.10-7.18 (m, 3H), 7.36 (s, 1H)
EXAMPLE 27
1-(2,4-dichloro-benzyl)-4-(4-methyl-pentoxy)-1H-pyridin-2-one
[0382] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 0.86 (d, 6H),
1.24-1.29 (m, 2H), 1.50-1.59 (m, 1H), 1.67-1.77 (m, 2H), 3.86 (t,
2H), 5.10 (s, 2H), 5.87-5.90 (m, 2H), 7.11-7.16 (m, 3H), 7.36 (s,
1H)
EXAMPLE 28
4-(but-3-enyloxy)-1-(2,4-dichloro-benzyl)-1H-pyridin-2-one
[0383] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 2.48 (q, 2H), 3.93
(t, 2H), 5.06-5.15 (m, 4H), 5.76-5.89 (m, 3H), 7.11-7.15 (m, 3H),
7.36 (s, 1H)
EXAMPLE 29
1-(2,4-dichloro-benzyl)-1H-pyridin-2-one
[0384] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 1.78-1.87 (m, 2H),
2.16 (q, 2H), 3.89 (t, 2H), 4.95-5.09 (m, 4H), 5.71-5.88 (m, 3H),
7.11-7.15 (m, 3H), 7.36 (s, 1H)
EXAMPLE 30
1-(2,4-dichloro-benzyl)-4-pentyloxy-1H-pyridin-2-one
[0385] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 0.93 (t, 3H),
1.33-1.44 (m, 4H), 1.72-1.79 (m, 2H), 3.91 (t, 2H), 5.14 (s, 2H),
7.16-7.22 (m, 3H), 7.40 (d, 1H)
EXAMPLE 31
[1-(2,4-dichloro-benzyl)-2-oxo-1,2-dihydro-pyridin-4-yloxy]-acetic
acid ethylester
[0386] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 3.77 (s, 3H), 4.54
(s, 2H), 5.09 (s, 2H), 5.77 (d, 1H), 5.99 (dd, 1H), 7.17-7.22 (m,
3H), 7.37 (s, 1H)
EXAMPLE 32
1-(2,4-dichloro-benzyl)-4-(3-methyl-butoxy)-1H-pyridin-2-one
[0387] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 0.87 (d, 6H),
1.54-1.76 (m, 3H), 3.86 (t, 2H), 5.00 (s, 2H), 5.79 (dd, 1H), 5.86
(d, 1H), 7.04 (d, 1H), 7.13-7.27 (m, 3H)
EXAMPLE 33
1-benzyl-4-pentyloxy-1H-pyridin-2-one
[0388] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 0.93 (t, 3H),
1.32-1.40 (m, 4H), 1.75-1.79 (m, 2H), 3.92 (t, 2H), 5.10 (s, 2H),
5.87-5.93 (m, 2H), 7.11 (d, 1H), 7.25-7.32 (m, 5H)
EXAMPLE 34
1-(2-chloro-benzyl)-4-pentyloxy-1H-pyridin-2-one
[0389] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 0.92 (t, 3H),
1.31-1.42 (m, 4H), 1.72-1.79 (m, 2H), 3.91 (t, 2H), 5.19 (S, 2H),
5.89-5.92 (m, 2H), 7.14-7.26 (m, 4H), 7.37-7.40 (m, 1H)
EXAMPLE 35
4-pentyloxy-1-propyl-1H-pyridin-2-one
[0390] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 0.90-0.96 (m, 6H),
1.28-1.38 (m, 4H), 1.67-1.80 (m, 4H), 3.82 (t, 2H), 3.89 (t, 2H),
5.87 (d, 2H), 7.07-7.10 (m, 1H)
EXAMPLE 36
1-butyl-4-pentyloxy-1H-pyridin-2-one
[0391] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 0.89-0.96 (m, 6H),
1.29-1.42 (m, 6H), 1.64-1.78 (m, 4H), 3.83-3.91 (m, 4H), 5.86-5.88
(m, 2H), 7.07-7.10 (m, 1H)
EXAMPLE 37
1-isobutyl-4-pentyloxy-1H-pyridin-2-one
[0392] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 0.91-0.93 (m, 9H),
1.33-1.39 (m, 4H), 1.71-1.78 (m, 2H), 2.10-2.19 (m, 1H), 3.65 (d,
2H), 3.89 (t, 2H), 5.84-5.87 (m, 2H), 7.05 (d, 1H)
EXAMPLE 38
1-(3-methyl-butyl)-4-pentyloxy-1H-pyridin-2-one
[0393] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 0.90-0.96 (m, 9H),
1.33-1.39 (m, 4H), 1.55-1.78 (m, 5H), 3.84-3.91 (m, 4H), 5.86-5.88
(m, 2H), 7.07-7.10 (m, 1H)
EXAMPLE 39
1-(2,4-dichloro-benzyl)-4-hexyloxy-1H-pyridin-2-one
[0394] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 0.90 (t, 3H),
1.25-1.34 (m, 4H), 1.71-1.80 (m, 2H), 3.91 (t, 2H), 5.14 (s, 2H),
5.91-5.93 (m, 2H), 7.14-7.23 (m, 3H), 7.40 (s, 1H)
EXAMPLE 40
1-(2,4-dichloro-benzyl)-4-heptoxy-1H-pyridin-2-one
[0395] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 0.75 (t, 3H),
1.09-1.54 (m, 8H), 1.71-1.80 (m, 2H), 3.91 (t, 2H), 5.13 (s, 2H),
5.86-5.92 (m, 2H), 7.14-7.22 (m, 3H), 7.40 (s, 1H)
EXAMPLE 41
1-(4-chloro-benzyl)-4-pentyloxy-1H-pyridin-2-one
[0396] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 0.92 (t, 3H),
1.33-1.42 (m, 4H), 1.71-1.80 (m, 2H), 3.90 (t, 2H), 5.04 (s, 2H),
5.87-5.91 (m, 2H), 7.08 (d, 1H), 7.20 (d, 2H), 7.30 (d, 2H)
EXAMPLE 42
4-aryloxy-1-(2,4-dichloro-benzyl)-1H-pyridin-2-one
[0397] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 4.48 (d, 2H), 5.14
(s, 2H), 5.32-5.45 (m, 2H), 5.94-6.07 (m, 3H), 7.18-7.20 (m, 3H),
7.41 (s, 1H)
EXAMPLE 43
1-(2,4-dichloro-benzyl)-4-(3-methoxy-propoxy)-1H-pyridin-2-one
[0398] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 2.01-2.07 (m, 2H),
3.35 (s, 3H), 3.52 (t, 2H), 4.02 (t, 2H), 5.14 (s, 2H), 5.91-5.94
(m, 2H), 7.16-7.20 (m, 3H), 7.41 (s, 1H)
EXAMPLE 44
1-(2,4-dichloro-benzyl)-4-(3-ethylamino-propoxy)-1H-pyridin-2-one
[0399] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 1.25-1.52 (m, 5H),
2.92-3.05 (m, 4H), 4.03 (t, 2H), 5.13 (s, 2H), 5.91-5.93 (m, 2H),
7.17-7.19 (m, 3H), 7.41 (s, 1H), 8.48 (br s, 1H)
EXAMPLE 45
1-(2,4-dichloro-benzyl)-4-(2-ethoxy-ethoxy)-1H-pyridin-2-one
[0400] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 1.25 (t, 3H), 3.58
(q, 2H), 3.77 (t, 2H), 4.08 (t, 2H), 5.14 (s, 2H), 5.92 (d, 1H),
5.99 (dd, 1H), 7.16-7.23 (m, 3H), 7.41 (s, 1H)
EXAMPLE 46
1-(3-methyl-but-2-enyl)-4-pentyloxy-1H-pyridin-2-one
[0401] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 0.92 (t, 3H),
1.33-1.38 (m, 4H), 1.71-1.73 (m, 2H), 1.76 (s, 6H), 3.89 (t, 2H),
4.47 (d, 2H), 5.27 (t, 1H), 5.87-5.88 (m, 2H), 7.10-7.13 (m,
1H)
EXAMPLE 47
5-(2-oxo-4-pentyloxy-2H-pyridin-1-ylmethyl)-furan-2-carboxyl acid
ethylester
[0402] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 0.92 (t, 3H),
1.33-1.44 (m, 7H), 1.73-1.80 (m, 2H), 3.89 (t, 2H), 4.34 (q, 2H),
5.09 (s, 2H), 5.86 (d, 1H), 5.92 (dd, 1H), 6.47 (d, 1H), 7.09 (d,
1H), 7.29 (d, 1H)
EXAMPLE 48
5-(2-oxo-4-pentyloxy-2H-pyridin-1-ylmethyl)-furan-2-carboxyl
acid
[0403] .sup.1H NMR (CD.sub.3OD, 300 MHz) .delta. 0.94 (t 3H),
1.37-1.45 (m, 4H), 1.73-1.80 (m, 2H), 3.97 (t, 2H), 5.13 (s, 2H),
5.89 (d, 1H), 6.11 (dd, 1H), 6.41 (d, 1H), 6.93 (d, 1H), 7.65 (d,
1H)
EXAMPLE 49
4-pentyloxy-1-thiazol-4-ylmethyl-1H-pyridin-2-one
[0404] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 0.92 (t, 3H),
1.32-1.44 (m, 4H), 1.70-1.80 (m, 2H), 3.89 (t, 2H), 5.22 (s, 2H),
5.88 (d, 1H), 5.92 (dd, 1H), 7.38-7.42 (m, 2H), 8.76 (s, 1H)
EXAMPLE 50
4-pentyloxy-1-pyridin-3-ylmethyl-1H-pyridin-2-one
[0405] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 0.93 (t, 3H),
1.32-1.45 (m, 4H), 1.74-1.83 (m, 2H), 3.96 (t, 2H), 5.55 (s, 2H),
6.29 (d, 1H), 6.50 (dd, 1H), 7.40 (s, 1H), 7.96 (d, 1H), 8.84 (d,
1H)
EXAMPLE 51
1-(2,4-dichloro-benzyl)-4-(4-methyl-pent-3-enyloxy)-1H-pyridin-2-one
[0406] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 1.65 (s, 3H), 1.73
(s, 3H), 2.46 (q, 2H), 3.89 (t, 2H), 5.14 (s, 2H), 5.91-5.94 (m,
2H), 7.15-7.13 (m, 3H), 7.27 (s, 1H), 7.41 (s, 1H)
EXAMPLE 52
1-(2,4-dichloro-benzyl)-4-(3-methoxy-propoxy)-1H-pyridin-2-one
[0407] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 0.88 (d, 6H),
1.18-1.26 (m, 4H), 1.37-1.77 (m, 5H), 3.92 (t, 2H), 5.14 (s, 2H),
5.91-5.93 (m, 2H), 7.15-7.23 (m, 3H), 7.41 (s, 1H)
EXAMPLE 53
1-(2,4-dichloro-benzyl)-4-phenetyloxy-1H-pyridin-2-one
[0408] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 3.09 (t, 2H), 4.15
(t 2H), 5.14 (s, 2H), 5.91-5.99 (m, 2H), 7.16-7.40 (m, 9H)
EXAMPLE 54
1-(2-methyl-benzyl)-4-pentyloxy-1H-pyridin-2-one
[0409] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 0.93 (t, 3H),
1.33-1.43 (m, 4H), 1.75-1.79 (m, 2H), 2.28 (s, 3H), 3.92 (t, 2H),
5.08 (s, 2H), 5.86 (dd, 1H), 5.94 (d, 1H), 6.93 (d, 1H), 7.03 (d,
1H), 7.15-7.23 (m, 3H)
EXAMPLE 55
4-pentyl-1-phenetyl-1H-pyridin-2-one
[0410] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 0.86 (t, 3H),
1.27-1.33 (m, 4H), 1.65-1.72 (m, 2H), 2.96 (t, 2H), 3.83 (t, 2H),
4.01 (t, 2H), 5.65 (dd, 1H), 5.83 (d, 1H), 6.65 (d, 1H), 7.08 (d,
1H), 7.13-7.25 (m, 3H)
EXAMPLE 56
1-(2,4-dichloro-5-fluoro-benzyl)-4-pentyloxy-1H-pyridin-2-one
[0411] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 0.93 (t, 3H),
1.31-1.43 (m, 4H), 1.73-1.80 (m, 2H), 3.92 (t, 2H), 5.10 (s, 2H),
5.92-5.96 (m, 2H), 7.02 (d, 1H), 7.16 (d, 1H), 7.44 (d, 1H)
EXAMPLE 57
1-(3,4-dichloro-benzyl)-4-pentyloxy-1H-pyridin-2-one
[0412] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 0.93 (t, 3H),
1.31-1.46 (m, 4H), 1.73-1.82 (m, 2H), 3.92 (t, 2H), 5.02 (s, 2H),
5.92-5.95 (m, 2H), 7.10-7.15 (m, 2H), 7.36-7.42 (m, 2H)
EXAMPLE 58
1-(3,4-difluoro-benzyl)-4-pentyloxy-1H-pyridin-2-one
[0413] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 0.93 (t, 3H),
1.32-1.43 (m, 4H), 1.73-1.80 (m, 2H), 3.92 (t, 2H), 5.02 (s, 2H),
5.91-5.94 (m, 2H), 7.03-7.17 (m, 4H)
EXAMPLE 59
4-(4-benzyloxy-butoxy)-1-(2,4-dichloro-benzyl)-1H-pyridin-2-one
[0414] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 1.68-1.94 (m, 4H),
3.54 (t, 2H), 3.96 (t, 2H), 4.53 (s, 2H), 5.15 (s, 2H), 5.90-5.93
(m, 2H), 7.16-7.42 (m, 9H)
EXAMPLE 60
1-(2,4-dichloro-benzyl)-4-(4-hydroxy-butoxy)-1H-pyridin-2-one
[0415] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 1.70-1.91 (m, 4H),
3.72 (t, 2H), 3.98 (t, 2H), 5.14 (s, 2H), 5.92-5.94 (m, 2H),
7.16-7.25 (m, 3H), 7.41 (s, 1H)
EXAMPLE 61
4-(5-benzyloxy-pentyloxy)-1-(2,4-dichloro-benzyl)-1H-pyridin-2-one
[0416] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 1.52-1.85 (m, 6H),
3.51 (t, 2H), 3.94 (t, 2H), 4.53 (s, 2H), 5.15 (s, 2H), 5.90-5.94
(m, 2H), 7.16-7.42 (m, 9H)
EXAMPLE 62
1-(2,4-dichloro-benzyl)-4-(5-hydroxy-pentyloxy)-1H-pyridin-2-one
[0417] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 1.44-1.83 (m, 6H),
3.70 (t, 2H), 3.93 (t, 2H), 5.14 (s, 2H), 5.91-5.92 (m, 2H),
7.15-7.20 (m, 3H), 7.41 (s, 1H)
EXAMPLE 63
1-(6-chloro-benzo[1,3]dioxol-5-ylmethyl)-4-pentyloxy-1H-pyridin-2-one
[0418] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 0.93 (t, 3H),
1.35-1.43 (m, 4H), 1.74-1.79 (m, 2H), 3.91 (t, 2H), 5.10 (s, 2H),
5.88-5.91 (m, 2H), 5.96 (s, 2H), 6.81 (s, 1H), 6.84 (s, 1H), 7.18
(dd, 1H)
EXAMPLE 64
1-(2,4-dichloro-benzyl)-4-(2-methyl-benzyloxy)-1H-pyridin-2-one
[0419] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 2.35 (s, 3H), 4.99
(s, 2H), 5.16 (s, 2H) 5.98 (dd, 1H), 6.08 (d, 1H), 7.20-7.42 (m,
8H)
EXAMPLE 65
1-(2,4-dichloro-benzyl)-4-(4-methyl-benzyloxy)-1H-pyridin-2-one
[0420] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 2.37 (s, 3H), 4.95
(s, 2H), 5.15 (s, 2H) 5.98 (dd, 1H), 6.03 (d, 1H), 7.18-7.30 (m,
8H)
EXAMPLE 66
1-(2-nitro-benzyl)-4-pentyloxy-1H-pyridin-2-one
[0421] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 0.93 (t, 3H),
1.34-1.43 (m, 4H), 1.73-1.82 (m, 2H), 3.93 (t, 2H), 5.46 (s, 2H),
5.93 (d, 1H), 5.98 (dd, 1H), 7.10 (d, 1H), 7.17 (d, 1H), 7.44 (t,
1H), 7.56 (t, 1H), 8.10 (d, 1H)
EXAMPLE 67
1-(2-amino-benzyl)-4-pentyloxy-1H-pyridin-2-one
[0422] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 0.91 (t, 3H),
1.30-1.39 (m, 4H), 1.69-1.76 (m, 2H), 3.89 (t, 2H), 4.75 (br s,
2H), 5.00 (s, 2H), 5.89-5.93 (m, 2H), 6.62-6.70 (m, 2H), 7.09-7.23
(m, 3H)
EXAMPLE 68
N-[2-(2-oxo-4-pentyloxy-2H-pyridin-1-ylmethyl)-phenyl]-acetamide
[0423] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 0.92 (t, 3H),
1.26-1.38 (m, 4H), 1.74-1.78 (m, 2H), 2.29 (s, 3H), 3.91 (t, 2H),
5.01 (s, 2H), 5.94 (d, 1H), 6.01 (dd, 1H), 7.08 (t, 1H), 7.31-7.38
(m, 3H), 8.20 (d, 1H), 10.56 (br s, 1H)
EXAMPLE 69
4-pentyloxy-1-(2-trifluoromethyl-benzyl)-1H-pyridin-2-one
[0424] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 0.94 (t, 3H),
1.31-1.42 (m, 4H), 1.75-1.81 (m, 2H), 3.95 (t, 2H), 5.32 (s, 2H),
5.93 (dd, 1H), 5.98 (d, 1H), 7.04 (d, 1H), 7.15 (d, 1H), 7.38 (t,
1H), 7.49 (t, 1H), 7.69 (d, 1H)
EXAMPLE 70
N-[4-(4-benzyloxy-2-oxo-2H-pyridin-1-ylmethyl)-phenyl]acetamide
[0425] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 2.18 (s, 3H), 4.99
(s, 2H), 5.04 (s, 2H) 5.98 (dd, 1H), 6.02 (d, 1H), 7.14-7.46 (m,
10H), 7.82 (br s, 1H)
EXAMPLE 71
1-(2,4-dichloro-benzyl)-4-(naphthalen-2-ylmethoxy)-1H-pyridin-2-one
[0426] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 5.15 (s, 2H), 5.16
(s, 2H), 5.99-6.09 (m, 2H), 7.18-7.55 (m, 7H), 7.83-7.90 (m,
4H)
EXAMPLE 72
1-naphthalen-2-ylmethyl-4-pentyloxy-1H-pyridin-2-one
[0427] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 0.92 (t, 3H),
1.35-1.43 (m, 4H), 1.73-1.76 (m, 2H), 3.91 (t, 2H), 5.24 (s, 2H),
5.84-5.96 (m, 2H), 7.13 (d, 1H), 7.26-7.49 (m, 3H), 7.70 (s, 1H),
7.79-7.83 (m, 3H)
EXAMPLE 73
4-benzyloxy-1-(6-chloro-benzo[1,3]dioxol-5-ylmethyl)-1H-pyridin-2-one
[0428] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 4.99 (s, 2H), 5.10
(s, 2H), 5.94-6.03 (m, 4H), 6.84 (d, 2H), 7.20 (d, 1H), 7.33-7.39
(m, 5H)
EXAMPLE 74
1-(6-chloro-benzo[1,3]dioxol-5-ylmethyl)-4-(3-methyl-butoxy)-1H-pyridin-2--
one
[0429] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 0.92 (d, 6H),
1.58-1.66 (m, 3H), 3.92 (t, 2H), 5.07 (s, 2H), 5.86 (dd, 1H), 5.90
(d, 1H), 5.93 (s, 2H), 6.80 (d, 2H), 7.14 (d, 1H)
EXAMPLE 75
1-(2-methyl-benzyl)-4-(3-methyl-butoxy)-1H-pyridin-2-one
[0430] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 0.92 (d, 6H), 1.63
(q, 2H), 1.72-1.81 (m, 1H), 3.93 (t, 2H), 5.05 (s, 2H), 5.82 (dd,
1H), 5.92 (d, 1H), 6.90 (d, 1H), 7.01 (d, 1H), 7.13-7.20 (m,
3H)
EXAMPLE 76
4-(3-methyl-butoxy)-1-(2-nitro-benzyl)-1H-pyridin-2-one
[0431] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 0.93 (d, 6H), 1.65
(q, 2H), 1.69-1.78 (m, 1H), 3.95 (t, 2H), 5.45 (s, 2H), 5.93-5.96
(m, 2H), 7.11 (d, 1H), 7.14 (d, 1H), 7.44 (t, 1H), 7.53 (t, 1H),
8.08 (d, 1H)
EXAMPLE 77
1-(2,4-dichloro-benzyl)-4-pentylamino-1H-pyridin-2-one
[0432] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 0.88 (t, 3H),
1.24-1.34 (m, 4H), 1.57-1.84 (m, 2H), 3.19 (br s, 1H), 3.47 (q,
2H), 5.03 (s, 2H), 5.56 (d, 1H), 7.15-7.38 (m, 4H)
EXAMPLE 78
1-(2,3-dichloro-benzyl)-4-pentyloxy-1H-pyridin-2-one
[0433] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 0.90 (t, 3H),
1.28-1.40 (m, 4H), 1.70-1.77 (m, 2H), 3.89 (t, 2H), 5.17 (s, 2H),
5.89-5.92 (m, 2H), 7.01 (d, 1H), 7.11-7.16 (m, 2H), 7.37 (d,
1H)
EXAMPLE 79
1-(2-methoxy-benzyl)-4-pentyloxy-1H-pyridin-2-one
[0434] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 0.90 (t, 3H),
1.27-1.36 (m, 4H), 1.68-1.77 (m, 2H), 3.83 (s, 3H), 3.87 (t, 2H),
5.05 (s, 2H), 5.81 (dd, 1H), 5.86 (d, 1H), 6.84-6.92 (m, 2H),
7.18-7.27 (m, 3H)
EXAMPLE 80
1-(2,3-dimethoxy-benzyl)-4-pentyloxy-1H-pyridin-2-one
[0435] .sup.1H NMR (CDCl.sub.3, 300 MHz) 60.89 (t 3H), 1.29-1.38
(m, 4H), 1.67-1.74 (m, 2H), 3.81-3.88 (m, 8H), 5.08 (s, 2H), 5.80
(dd, 1H), 5.86 (d, 1H), 6.82-6.87 (m, 2H), 6.98 (t, 1H), 7.18 (d,
1H)
EXAMPLE 81
4-(5-benzyloxy-pentyloxy)-1-(6-chloro-benzo[1,3]dioxol-5-ylmethyl)-1H-pyri-
din-2-one
[0436] .sup.1H NMR (CD.sub.3OD, 300 MHz) .delta. 1.47-1.53 (m, 2H),
1.61-1.66 (m, 2H), 1.74-1.78 (m, 2H), 3.48 (t, 2H), 3.96 (t, 2H),
4.45 (s, 2H), 5.06 (s, 2H), 5.90 (s, 1H), 5.94 (s, 2H), 6.06 (dd,
1H), 6.61 (s, 1H), 6.90 (s, 1H), 7.22-7.29 (m, 5H), 7.42 (d,
1H)
EXAMPLE 82
1-(2-chloro-benzyl)-4-(3-methyl-butoxy)-1H-pyridin-2-one
[0437] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 0.93 (d, 6H),
1.60-1.82 (m, 3H), 3.94 (t, 2H), 5.17 (s, 2H), 5.86-5.94 (m, 2H),
7.12-7.40 (m, 5H)
EXAMPLE 83
1-(3,4-dichloro-benzyl)-4-(3-methyl-butoxy)-1H-pyridin-2-one
[0438] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 0.92 (d, 6H), 1.63
(q, 2H), 1.72-1.81 (m, 1H), 3.92 (t, 2H), 4.99 (s, 2H), 5.87-5.90
(m, 2H), 7.05-7.12 (m, 2H), 7.33-7.38 (m, 2H)
EXAMPLE 84
1-(2,4-dichloro-5-fluoro-benzyl)-4-(3-methyl-butoxy)-1H-pyridin-2-one
[0439] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 0.92 (d, 6H), 1.64
(q, 2H), 1.71-1.82 (m, 1H), 3.93 (t, 2H), 5.08 (s, 2H), 5.90-5.92
(m, 2H), 7.00 (d, 1H), 7.12-7.15 (m, 1H), 7.42 (d, 1H)
EXAMPLE 85
1-benzyl-4-(3-methyl-butoxy)-1H-pyridin-2-one
[0440] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 0.95 (d, 6H),
1.59-1.78 (m, 3H), 3.93 (t, 2H), 5.08 (s, 2H), 5.83-5.93 (m, 2H),
7.07-7.36 (m, 6H)
EXAMPLE 86
1-(4-chloro-benzyl)-4-(3-methyl-butoxy)-1H-pyridin-2-one
[0441] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 0.92 (d, 6H), 1.62
(q, 2H), 1.71-1.80 (m, 1H), 3.91 (t, 2H), 5.01 (s, 2H), 5.85 (dd,
1H), 5.89 (d, 1H), 7.06 (d, 1H), 7.19 (d, 2H), 7.27 (d, 2H)
EXAMPLE 87
1-(2,4-dichloro-benzyl)-4-pentyloxy-1H-pyrimidin-2-one
[0442] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 0.88 (t, 3H),
1.32-1.36 (m, 4H), 1.61-1.73 (m, 2H), 4.33 (t, 2H), 5.07 (s, 2H),
5.83 (d, 1H), 7.22 (d, 1H), 7.35-7.45 (m, 3H)
EXAMPLE 88
1-(2,4-dichloro-benzyl)-4-(4-methyl-pentyloxy)-1H-pyrimidin-2-one
[0443] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 0.89 (d, 6H),
1.20-1.76 (m, 5H), 4.34 (t, 2H), 5.09 (s, 2H), 5.85 (d, 1H), 7.22
(d, 1H), 7.26-7.47 (m, 3H)
EXAMPLE 89
1-(2,4-dichloro-benzyl)-4-phenoxy-1H-pyrimidin-2-one
[0444] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 5.11 (d, 2H), 6.07
(d, 1H), 7.12-7.65 (m, 9H)
EXAMPLE 90
4-(butyl-methyl-amino)-1-(2,4-dichloro-benzyl)-1H-pyrimidin-2-one
[0445] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 0.90 (t 3H),
1.19-1.56 (m, 4H), 2.81-3.11 (m, 3H), 3.22-3.27 (m, 1H), 3.59-3.62
(m, 1H), 4.98 (s, 2H), 5.72-5.75 (m, 1H), 7.12-7.31 (m, 4H)
EXAMPLE 91
1-(2,4-dichloro-benzyl)-4-(2-diethylamino-ethoxy)-1H-pyrimidin-2-one
[0446] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 1.04 (t, 6H), 2.62
(q, 4H), 2.84 (t, 2H), 4.46 (t, 2H), 5.09 (s, 2H), 5.90 (d, 1H),
7.21-7.54 (m, 4H)
EXAMPLE 92
4-butoxy-1-(2,4-dichloro-benzyl)-1H-pyrimidin-2-one
[0447] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 0.95 (t, 3H),
1.39-1.46 (m, 2H), 1.69-1.74 (m, 2H), 4.37 (t, 2H), 5.10 (s, 2H),
5.87 (d, 1H), 7.23-7.48 (m, 4H)
EXAMPLE 93
1-(2,6-dichloro-benzyl)-4-pentyloxy-1H-pyridin-2-one
[0448] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 0.91 (t, 3H),
1.32-1.44 (m, 4H), 1.70-1.80 (m, 2H), 3.90 (t, 2H), 5.37 (s, 2H),
5.79 (dd, 1H), 5.91 (d, 1H), 6.71 (d, 1H), 7.25-7.41 (m, 3H)
EXAMPLE 94
1-(2-chloro-6-fluoro-benzyl)-4-pentyloxy-1H-pyridin-2-one
[0449] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 0.91 (t, 3H),
1.30-1.44 (m, 4H), 1.70-1.77 (m, 2H), 3.89 (t, 2H), 5.24 (s, 2H),
5.82 (dd, 1H), 5.88 (d, 1H), 6.92 (d, 1H), 7.05 (t, 1H), 7.24-7.33
(m, 2H)
EXAMPLE 95
1-(2-methyl-3-nitro-benzyl)-4-pentyloxy-1H-pyridin-2-one
[0450] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 0.92 (t, 3H),
1.33-1.43 (m, 4H), 1.75 (m, 2H), 2.40 (s, 3H), 3.92 (t, 2H), 5.13
(s, 2H), 5.92-5.95 (m, 2H), 6.98 (dd, 1H), 7.16 (d, 1H), 7.28 (t,
1H), 7.69 (d, 1H)
EXAMPLE 96
1-(3-amino-2-methyl-benzyl)-4-pentyloxy-1H-pyridin-2-one
[0451] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 0.92 (t, 3H),
1.33-1.43 (m, 4H), 1.71-1.80 (m, 2H), 2.01 (s, 3H), 3.72 (s, 2H),
3.91 (t, 2H), 5.05 (s, 2H), 5.81 (dd, 1H), 5.92 (d, 1H), 6.56 (d,
1H), 6.69 (d, 1H), 6.90 (d, 1H), 7.01 (t, 1H)
EXAMPLE 97
1-(4-methoxy-3,5-dimethyl-pyridin-2-ylmethyl)-4-pentyloxy-1H-pyridin-2-one
[0452] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 0.92 (t, 3H),
1.30-1.41 (m, 4H), 1.70-1.77 (m, 2H), 2.23 (s, 3H), 2.30 (s, 3H),
3.75 (s, 3H), 3.89 (t, 2H), 5.16 (s, 2H), 5.85-5.88 (m, 2H),
7.28-7.30 (m, 1H), 8.19 (s, 1H)
EXAMPLE 98
1-(6-chloro-benzo[1,3]dioxol-5-ylmethyl)-4-(5-hydroxy-pentyloxy)-1H-pyridi-
n-2-one
[0453] .sup.1H NMR (CD.sub.3OD, 300 MHz) .delta. 1.48-1.58 (m, 4H),
1.75-1.80 (m, 2H), 3.54 (t, 2H), 3.97 (t, 2H), 5.06 (s, 2H), 5.89
(d, 1H), 5.94 (s, 2H), 6.07 (dd, 1H), 6.61 (s, 1H), 6.90 (s, 1H),
7.43 (d, 1H)
EXAMPLE 99
1-(2-methoxy-5-nitro-benzyl)-4-pentyloxy-1H-pyridin-2-one
[0454] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 0.92 (t, 3H),
1.36-1.44 (m, 4H), 1.74-1.80 (m, 2H), 3.91 (t, 2H), 3.97 (S, 3H),
5.07 (s, 2H), 5.90-5.95 (m, 2H), 7.17 (d, 1H), 7.21 (d, 1H), 8.03
(d, 1H), 8.19 (dd, 1H)
EXAMPLE 100
1-(5-amino-2-methoxy-benzyl)-4-pentyloxy-1H-pyridin-2-one
[0455] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 0.92 (t, 3H),
1.24-1.39 (m, 4H), 1.73-1.78 (m, 2H), 3.79 (s, 2H), 3.90 (t, 2H),
5.02 (s, 2H), 5.83 (dd, 1H), 5.89 (d, 1H), 6.59-6.74 (m, 3H),
7.23-7.27 (m, 3H)
EXAMPLE 101
1-(2-ethyl-benzyl)-4-pentyloxy-1H-pyridin-2-one
[0456] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 0.93 (t, 3H), 1.18
(t, 3H), 1.34-1.43 (m, 4H), 1.73-1.79 (m, 2H), 2.63 (q, 2H), 3.93
(t, 2H), 5.12 (s, 2H), 5.84 (dd, 1H), 5.94 (d, 1H), 6.92 (d, 1H),
7.05 (d, 1H), 7.16-7.32 (m, 3H)
EXAMPLE 102
1-(2-chloro-5-nitro-benzyl)-4-pentyloxy-1H-pyridin-2-one
[0457] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 0.93 (t, 3H),
1.32-1.46 (m, 4H), 1.72-1.82 (m, 2H), 3.94 (t, 2H), 5.19 (s, 2H),
5.94 (dd, 1H), 6.00 (d, 1H), 7.18 (d, 1H), 7.55 (d, 1H), 7.96 (d,
1H), 9.09 (dd, 1H)
EXAMPLE 103
1-(5-amino-2-chloro-benzyl)-4-pentyloxy-1H-pyridin-2-one
[0458] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 0.93 (t, 3H),
1.31-1.43 (m, 4H), 1.72-1.79 (m, 2H), 3.91 (t, 2H), 5.11 (s, 2H),
5.87-5.91 (m, 2H), 6.52-6.55 (m, 2H), 7.11-7.18 (m, 2H)
EXAMPLE 104
1-(4-methoxy-2,3-dimethyl-benzyl)-4-pentyloxy-1H-pyridin-2-one
[0459] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 0.93 (t, 3H),
1.31-1.42 (m, 4H), 1.72-1.81 (m, 2H), 2.12 (s, 3H), 2.16 (s, 3H),
3.82 (s, 3H), 3.91 (t, 2H), 5.04 (s, 2H), 5.80 (dd, 1H), 5.93 (d,
1H), 6.71 (d, 1H), 6.85 (d, 1H), 6.97 (d, 1H)
EXAMPLE 105
1-(2-methyl-pyridin-3-ylmethyl)-4-pentyloxy-1H-pyridin-2-one
[0460] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 0.93 (t, 3H),
1.32-1.47 (m, 4H), 1.73-1.83 (m, 2H), 2.56 (s, 3H), 3.93 (t, 2H),
5.09 (s, 2H), 5.91-5.94 (m, 2H), 7.00 (d, 1H), 7.08-7.13 (m, 1H),
7.26-7.28 (m, 1H), 8.43 (d, 1H)
EXAMPLE 106
N-[4-chloro-3-(2-oxo-4-pentyloxy-2H-pyridin-1-ylmethyl)-phenyl]-acetamide
[0461] .sup.1HNMR(CDCl.sub.3, 300 MHz) .delta. 0.93 (t, 3H),
1.29-1.45 (m, 4H), 1.71-1.78 (m, 2H), 2.10 (s, 3H), 3.87 (t, 2H),
5.16 (s, 2H), 5.89 (d, 1H), 5.99 (dd, 1H), 7.26-7.33 (m, 3H), 7.77
(d, 1H), 8.43 (br s, 1H)
EXAMPLE 107
1-(2,4-dichloro-benzyl)-4-(3-dimethylamino-propoxy)-1H-pyridin-2-one
[0462] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 1.87-1.97 (m, 2H),
2.25 (s, 6H), 2.40 (t, 2H), 4.42 (t, 2H), 5.10 (s, 2H), 5.87 (d,
1H), 7.23-7.49 (m, 4H)
EXAMPLE 108
1-(2,4-dichloro-benzyl)-4-(4-dimethylamino-butoxy)-1H-pyridin-2-one
[0463] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 1.52-1.81 (m, 4H),
2.22 (s, 6H), 2.29 (t, 2H), 4.38 (t, 2H), 5.10 (s, 2H), 5.86 (d,
1H), 7.23-7.48 (m, 4H)
EXAMPLE 109
1-(2,4-dichloro-benzyl)-4-(6-dimethylamino-hexyloxy)-1H-pyrimidin-2-one
[0464] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 1.34-1.78 (m, 8H),
2.24-2.30 (m, 8H), 4.35 (t, 2H), 5.10 (s, 2H), 5.86 (d, 1H),
7.23-7.47 (m, 4H)
EXAMPLE 110
1-(2,4-dimethyl-benzyl)-4-pentyloxy-1H-pyridin-2-one
[0465] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 0.92 (t, 3H),
1.33-1.42 (m, 4H), 1.71-1.76 (m, 2H), 2.22 (s, 3H), 2.31 (s, 3H),
3.91 (t, 2H), 5.03 (s, 2H), 5.83 (dd, 1H), 5.92 (d, 1H), 6.89-7.20
(m, 4H)
EXAMPLE 111
1-(2-chloro-5-trifluoromethyl-benzyl)-4-pentyloxy-1H-pyridin-2-one
[0466] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 0.93 (t, 3H),
1.34-1.46 (m, 4H), 1.74-1.83 (m, 2H), 3.93 (t, 2H), 5.21 (s, 2H),
5.94-6.15 (m, 2H), 7.17 (d, 1H), 7.43-7.54 (m, 3H)
EXAMPLE 112
1-(2-hydroxy-benzyl)-4-pentyloxy-1H-pyridin-2-one
[0467] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 0.91 (t, 3H),
1.29-1.43 (m, 4H), 1.70-1.79 (m, 2H), 3.90 (t, 2H), 4.99 (s, 2H),
5.97 (d, 1H), 6.04 (dd, 1H), 6.83 (t, 1H), 6.95 (dd, 1H), 7.19-7.24
(m, 2H), 7.38 (d, 1H), 10.45 (br s, 1H)
EXAMPLE 113
4-(3-cyclo-propoxy)-1-(2,4-dichloro-benzyl)-1H-pyrimidin-2-one
[0468] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 1.27-1.25 (m, 2H),
1.51-1.82 (m, 9H), 4.37 (t, 2H), 5.10 (s, 2H), 5.85 (d, 1H), 7.22
(d, 1H), 7.38-7.47 (m, 3H)
EXAMPLE 114
1-(2,4-dichloro-benzyl)-4-(3-methyl-pentyloxy)-1H-pyrimidin-2-one
[0469] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 0.85-2.03 (m, 1H),
4.39 (t, 2H), 5.10 (s, 2H), 5.85 (d, 1H), 7.22-7.47 (m, 4H)
EXAMPLE 115
1-(2,4-dichloro-benzyl)-4-hex-4-enyloxy-1H-pyrimidin-2-one
[0470] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 1.25-2.10 (m, 7H),
4.35 (t, 2H), 5.10 (s, 2H), 5.40-5.46 (m, 2H), 5.86 (d, 1H),
7.23-7.47 (m, 4H)
EXAMPLE 116
4-(2-cyclopropyl-ethoxy)-1-(2,4-dichloro-benzyl)-1H-pyrimidin-2-one
[0471] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 0.42-0.96 (m, 3H),
1.25-1.66 (m, 4H), 4.43 (t, 2H), 5.10 (s, 2H), 5.87 (d, 1H),
7.22-7.47 (m, 4H)
EXAMPLE 117
1-(2,4-dichloro-benzyl)-4-(3-methyl-pentyloxy)-1H-pyridin-2-one
[0472] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 0.85-0.91 (m, 6H),
1.17-1.24 (m, 1H), 1.33-1.39 (m, 1H), 1.51-1.58 (m, 2H), 1.78-1.80
(m, 1H), 3.93 (t, 2H), 5.12 (s, 2H), 5.88-5.92 (m, 2H), 7.14-7.20
(m, 3H), 7.38 (s, 1H)
EXAMPLE 118
1-(2,4-dichloro-benzyl)-4-(5-morpholin-4-yl-pentyloxy)-1H-pyridin-2-one
[0473] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 1.46-1.61 (m, 4H),
1.75-1.84 (m, 2H), 2.36 (t, 2H), 2.44 (br s, 4H), 3.73 (t, 4H),
3.92 (t, 2H), 5.14 (s, 2H), 5.90-5.92 (m, 2H), 7.16-7.23 (m, 3H),
7.41 (s, 1H)
EXAMPLE 119
1-(2-chloro-5-methoxy-benzyl)-4-pentyloxy-1H-pyridin-2-one
[0474] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 0.93 (t, 3H),
1.33-1.43 (m, 4H), 1.72-1.79 (m, 2H), 3.74 (s, 3H), 3.91 (t, 2H),
5.15 (s, 2H), 5.88-5.93 (m, 2H), 6.76-6.79 (m, 2H), 7.15 (d, 1H),
7.27 (d, 1H)
EXAMPLE 120
1-(2-chloro-5-ethoxy-benzyl)-4-pentyloxy-1H-pyridin-2-one
[0475] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 0.93 (t 3H),
1.25-1.40 (m, 7H), 1.72-1.81 (m, 2H), 3.89-3.99 (m, 4H), 5.15 (s,
2H), 5.89-5.92 (m, 2H), 6.75-6.77 (m, 2H), 7.15 (d, 1H), 7.26 (d,
1H)
EXAMPLE 121
1-(2-chloro-5-propoxy-benzyl)-4-pentyloxy-1H-pyridin-2-one
[0476] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 0.93 (t, 3H), 1.00
(t, 3H), 1.33-1.43 (m, 4H), 1.70-1.81 (m, 4H), 3.84 (t, 2H), 3.92
(t, 2H), 5.15 (s, 2H), 5.88-5.93 (m, 2H), 6.74-6.78 (m, 2H), 7.15
(d, 1H), 7.26 (d, 1H)
EXAMPLE 122
1-[2-chloro-5-(2-hydroxy-ethoxy)-benzyl]-4-pentyloxy-1H-pyridin-2-one
[0477] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 0.90 (t, 3H),
1.25-1.43 (m, 4H), 1.72-1.79 (m, 2H), 2.13 (t, 1H), 3.91 (t, 4H),
4.01 (t, 2H), 5.15 (s, 2H), 5.86-5.92 (m, 2H), 6.76-6.83 (m, 2H),
7.18 (d, 1H), 7.28 (d, 1H)
EXAMPLE 123
[4-chloro-3-(2-oxo-4-pentyloxy-2H-pyridin-1-ylmethyl)-oxy]-acetonitrile
[0478] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 0.93 (t, 3H),
1.33-1.43 (m, 4H), 1.73-1.82 (m, 2H), 3.92 (t, 2H), 4.71 (s, 2H),
5.16 (s, 2H), 5.92-5.95 (m, 2H), 6.84-6.88 (m, 2H), 7.20 (d, 1H),
7.35 (dd, 1H)
EXAMPLE 124
1-[5-(2-amino-ethoxy)-2-chloro-benzyl]-4-pentyloxy-1H-pyridin-2-one
[0479] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 0.93 (t, 3H)
1.41-1.44 (m, 4H), 1.78-1.82 (m, 2H), 3.93 (t, 2H), 4.01 (t, 4H),
5.17 (s, 2H), 5.96 (d, 1H), 7.13 (dd, 1H), 6.60 (s, 1H), 6.90 (d,
1H), 7.34 (d, 1H), 7.49 (d, 1H)
EXAMPLE 125
N-[2-methyl-3-(2-oxo-4-pentyloxy-2H-pyridin-1-ylmethyl)-phenyl]-acetamide
[0480] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 0.93 (t, 3H),
1.34-1.44 (m, 4H), 1.73-1.82 (m, 2H), 2.07 (s, 3H), 2.22 (s, 3H),
3.92 (t, 2H), 5.05 (s, 2H), 5.89 (dd, 1H), 5.93 (d, 1H), 6.84 (d,
1H), 6.94 (d, 1H), 7.18 (t, 1H), 7.49 (br s, 1H), 7.56 (d, 1H)
EXAMPLE 126
1-(2-methyl-3-methylamino-benzyl)-4-phenyloxy-1H-pyridin-2-one
[0481] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 0.92 (t, 3H),
1.27-1.40 (m, 4H), 1.73-1.78 (m, 2H), 1.98 (s, 3H), 2.90 (s, 3H),
3.69 (br s, 1H), 3.90 (t, 2H), 5.07 (s, 2H), 5.80 (dd, 1H), 5.93
(d, 1H), 6.57 (d, 1H), 6.65 (d, 1H), 6.89 (d, 1H), 7.16 (t, 1H)
EXAMPLE 127
1-(3-dimethylamino-2-methyl-benzyl)-4-phenyloxy-1H-pyridin-2-one
[0482] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 0.93 (t, 3H),
1.36-1.43 (m, 4H), 1.75-1.79 (m, 2H), 2.22 (s, 3H), 2.69 (s, 6H),
3.92 (t, 2H), 5.07 (s, 2H), 5.86 (dd, 1H), 5.95 (d, 1H), 6.72 (d,
1H), 6.93 (d, 1H), 7.05 (d, 1H), 7.15 (t, 1H)
EXAMPLE 128
1-(3-ethylamino-2-methyl-benzyl)-4-pentyloxy-1H-pyridin-2-one
[0483] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 0.92 (t, 3H), 1.31
(t, 3H), 1.33-1.42 (m, 4H), 1.71-1.78 (m, 2H), 1.97 (s, 3H), 3.19
(q, 2H), 3.48 (br s, 1H), 3.90 (t, 2H), 5.06 (s, 2H), 5.79 (dd,
1H), 5.93 (d, 1H), 6.56 (d, 1H), 6.65 (d, 1H), 6.89 (d, 1H), 7.13
(t, 1H)
EXAMPLE 129
1-(3-diethylamino-2-methyl-benzyl)-4-pentyloxy-1H-pyridin-2-one
[0484] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 0.96 (t, 9H),
1.34-1.44 (m, 4H), 1.75-1.80 (m, 2H), 2.21 (s, 3H), 2.95 (q, 4H),
3.92 (t, 2H), 5.08 (s, 2H), 5.87-5.95 (m, 2H), 6.73 (d, 1H),
6.95-7.16 (m, 3H)
EXAMPLE 130
1-(2-methyl-3-propylamino-benzyl)-4-pentyloxy-1H-pyridin-2-one
[0485] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 0.93 (t, 3H), 1.02
(t, 3H), 1.33-1.42 (m, 4H), 1.66-1.80 (m, 4H), 1.97 (s, 3H), 3.12
(t, 2H), 3.57 (br s, 1H), 3.91 (t, 2H), 5.06 (s, 2H), 5.80 (dd,
1H), 5.93 (d, 1H), 6.55 (d, 1H), 6.65 (d, 1H), 6.90 (d, 1H), 7.13
(t, 1H)
EXAMPLE 131
1-(3-dipropylamino-2-methyl-benzyl)-4-pentyloxy-1H-pyridin-2-one
[0486] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 0.83 (t, 6H), 0.93
(t, 3H), 1.34-1.47 (m, 8H), 1.75-1.80 (m, 2H), 2.22 (s, 3H),
2.82-2.87 (m, 4H), 3.93 (t, 2H), 5.07 (s, 2H), 5.87 (dd, 1H), 5.96
(d, 1H), 6.69 (d, 1H), 6.94 (d, 1H), 7.07-7.15 (m, 2H)
EXAMPLE 132
1-[3-(2-hydroxy-ethylamino)-2-methyl-benzyl]-4-pentyloxy-1H-pyridin-2-one
[0487] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 0.92 (t, 3H),
1.32-1.41 (m, 4H), 1.71-1.78 (m, 2H), 1.83 (br s, 1H), 2.01 (s,
3H), 3.34 (t, 2H), 3.90 (t, 4H), 4.02 (br s, 1H), 5.06 (s, 2H),
5.81 (dd, 1H), 5.92 (d, 1H), 6.57 (d, 1H), 6.67 (d, 1H), 6.89 (d,
1H), 7.12 (t, 1H)
EXAMPLE 133
1-(2-chloro-5-methoxy-4-nitro-benzyl)-4-pentyloxy-1H-pyridin-2-one
[0488] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 0.94 (t, 3H),
1.37-1.44 (m, 4H), 1.76-1.81 (m, 2H), 3.91 (s, 3H), 3.93 (t, 2H),
5.20 (s, 2H), 5.93 (d, 1H), 5.97 (dd, 1H), 7.18 (s, 1H), 7.26 (d,
1H), 7.93 (s, 1H)
EXAMPLE 134
1-(4-amino-2-chloro-5-methoxy-benzyl)-4-pentyloxy-1H-pyridin-2-one
[0489] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 0.92 (t, 3H),
1.32-1.42 (m, 4H), 1.71-1.78 (m, 2H), 3.81 (t, 3H), 3.87-3.93 (m,
4H), 5.09 (s, 2H), 5.85 (dd, 1H), 5.90 (d, 1H), 6.69 (s, 1H), 6.91
(s, 1H), 7.21 (d, 1H)
EXAMPLE 135
N-[5-chloro-2-methoxy-4-(2-oxo-4-pentyloxy-2H-pyridin-1-ylmethyl)-phenyl]--
acetamide
[0490] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 0.92 (t, 3H),
1.35-1.42 (m, 4H), 1.74-1.78 (m, 2H), 2.21 (s, 3H), 3.84 (s, 3H),
3.90 (t, 2H), 5.15 (s, 2H), 5.88-5.93 (m, 2H), 7.04 (s, 1H), 7.29
(d, 1H), 7.77 (br s, 1H), 8.46 (s, 1H)
EXAMPLE 136
1-(2-chloro-5-methoxy-4-methylamino-benzyl)-4-pentyloxy-1H-pyridin-2-one
[0491] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 0.93 (t, 3H),
1.30-1.43 (m, 4H), 1.70-1.77 (m, 2H), 2.85 (s, 3H), 3.81 (s, 3H),
3.92 (t, 2H), 4.95 (s, 2H), 5.89-6.03 (m, 2H), 6.53 (s, 1H), 6.89
(s, 1H), 7.28 (d, 1H)
EXAMPLE 137
1-(2-chloro-4-dimethylamino-5-methoxy-benzyl)-4-pentyloxy-1H-pyridin-2-one
[0492] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 0.95 (t, 3H),
1.40-1.44 (m, 4H), 1.75-1.81 (m, 2H), 2.76 (s, 6H), 3.80 (s, 3H),
3.99 (t, 2H), 5.14 (s, 2H), 5.95 (d, 1H), 6.10 (dd, 1H), 6.85 (s,
1H), 7.00 (s, 1H), 7.47 (d, 1H)
EXAMPLE 138
1-(2-chloro-4-ethylamino-5-methoxy-benzyl)-4-pentyloxy-1H-pyridin-2-one
[0493] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 0.92 (t, 3H), 1.28
(t, 3H), 1.36-1.41 (m, 4H), 1.71-1.77 (m, 2H), 3.13 (t, 2H), 3.80
(s, 3H), 3.89 (t, 2H), 4.23 (br s, 1H), 5.10 (s, 2H), 5.84 (dd,
1H), 5.90 (d, 1H), 6.52 (s, 1H), 6.87 (s, 1H), 7.22 (d, 1H)
EXAMPLE 139
1-(2-chloro-5-methoxy-4-propylamino-benzyl)-4-pentyloxy-1H-pyridin-2-one
[0494] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 0.92 (t, 3H), 1.00
(t, 3H), 1.34-1.41 (m, 4H), 1.62-1.77 (m, 4H), 3.05 (t, 2H), 3.80
(s, 3H), 3.89 (t, 2H), 4.31 (br s, 1H), 5.09 (s, 2H), 5.83 (dd,
1H), 5.89 (d, 1H), 6.51 (s, 1H), 6.86 (s, 1H), 7.21 (d, 1H)
EXAMPLE 140
1-[2-chloro-4-(2-hydroxy-ethylamino)-5-methoxy-benzyl]-4-pentyloxy-1H-pyri-
din-2-one
[0495] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 0.92 (t, 3H),
1.32-1.42 (m, 4H), 1.70-1.77 (m, 2H), 1.96 (br s, 1H), 3.30 (t,
2H), 3.79 (s, 3H), 3.82-3.91 (m, 4H), 4.73 (br s, 1H), 5.09 (s,
2H), 5.85 (dd, 1H), 5.90 (d, 1H), 6.57 (s, 1H), 6.88 (s, 1H), 7.21
(d, 1H)
EXAMPLE 141
1-(4-amino-6-chloro-3-methoxy-2-nitro-benzyl)-4-pentyloxy-1H-pyridin-2-one
[0496] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 0.91 (t, 3H),
1.28-1.41 (m, 4H), 1.69-1.79 (m, 2H), 3.84 (s, 3H), 3.88 (t, 2H),
4.35 (br s, 2H), 4.96 (s, 2H), 5.82-5.85 (m, 2H), 6.92-7.02 (m,
2H)
EXAMPLE 142
1-(2,4-diamino-6-chloro-3-methoxy-benzyl)-4-pentyloxy-1H-pyridin-2-one
[0497] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 0.92 (t, 3H),
1.30-1.39 (m, 4H), 1.73-1.77 (m, 2H), 3.69 (s, 3H), 3.79 (br s,
2H), 3.89 (t, 2H), 5.16 (s, 2H), 5.30 (br s, 2H), 5.88-5.94 (m,
2H), 6.17 (s, 1H), 7.56 (d, 1H)
EXAMPLE 143
1-(2,5-dichloro-6-methoxy-pyrimidin-4-ylmethyl)-4-pentyloxy-1H-pyridin-2-o-
ne
[0498] H NMR (CDCl.sub.3, 300 MHz) .delta. 0.93 (t 3H), 1.34-1.45
(m, 4H), 1.73-1.82 (m, 2H), 3.92 (t, 2H), 4.08 (s, 3H), 5.14 (s,
2H), 5.86 (d, 1H), 5.96 (dd, 1H), 7.19 (d, 1H)
EXAMPLE 144
1-(2,4-dichloro-benzenesulfonyl)-4-pentyloxy-1H-pyridin-2-one
[0499] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 0.90 (t, 3H),
1.32-1.40 (m, 4H), 1.72-1.79 (m, 2H), 3.89 (t, 2H), 5.60 (d, 1H),
6.05 (dd, 1H), 7.47-7.51 (m, 2H), 7.95 (d, 1H), 8.35 (d, 1H)
EXAMPLE 145
1-(4-methanesulfonyl-benzyl)-4-pentyloxy-1H-pyridin-2-one
[0500] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 0.94 (t, 3H),
1.34-1.45 (m, 4H), 1.74-1.83 (m, 2H), 3.04 (s, 3H), 3.94 (t, 2H),
5.22 (s, 2H), 5.93 (d, 1H), 5.99 (dd, 1H), 7.20 (d, 1H), 7.32 (d,
1H), 7.76 (dd, 1H), 7.97 (d, 1H)
EXAMPLE 146
1-(4-amino-2-chloro-5-hydroxy-benzyl)-4-pentyloxy-1H-pyridin-2-one
[0501] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 0.91 (t, 3H),
1.29-1.41 (m, 4H), 1.66-1.75 (m, 2H), 3.78 (t, 2H), 5.13 (s, 2H),
5.85 (d, 1H), 5.94 (dd, 1H), 6.68 (s, 1H), 7.18 (s, 1H), 7.44 (d,
1H)
EXAMPLE 147
4-(4-bromo-butoxy)-1-(2,4-dichloro-benzyl)-1H-pyridin-2-one
[0502] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 10.88-2.08 (m,
4H), 3.46 (t, 2H), 3.95 (t, 2H), 5.13 (s, 2H), 5.88-5.92 (m, 2H),
7.16-7.24 (m, 3H), 7.40 (s, 1H)
EXAMPLE 148
4-[1-(2,4-dichloro-benzyl)-2-oxo-1,2-dihydro-pyridin-4-yloxy]-butylammoniu-
m
[0503] .sup.1H NMR (CD.sub.3OD, 300 MHz) .delta. 1.82-1.90 (m, 4H),
3.00 (t, 2H), 4.07 (t, 2H), 5.19 (s, 2H), 5.97 (s, 1H), 6.14 (dd,
1H), 7.05 (d, 1H), 7.31 (dd, 1H), 7.53-7.57 (m, 2H)
EXAMPLE 149
1-(5-chloro-2,6-dimethoxy-pyrimidin-4-ylmethyl)-4-pentyloxy-1H-pyridin-2-o-
ne
[0504] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 0.93 (t, 3H),
1.32-1.40 (m, 4H), 1.73-1.80 (m, 2H), 3.80 (s, 3H), 3.91 (t, 2H),
4.04 (s, 3H), 5.15 (s, 2H), 5.89 (d, 1H), 5.93 (dd, 1H), 7.16 (d,
1H)
EXAMPLE 150
1-(2-amino-5-chloro-6-methoxy-pyrimidin-4-ylmethyl)-4-pentyloxy-1H-pyridin-
-2-one
[0505] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 0.93 (t, 3H),
1.32-1.43 (m, 4H), 1.73-1.80 (m, 2H), 3.92 (t, 2H), 3.95 (s, 3H),
4.81 (br s, 2H), 5.08 (s, 2H), 5.90-5.93 (m, 2H), 7.10 (d, 1H)
EXAMPLE 151
1-(6-amino-2,5-dichloro-pyrimidin-4-ylmethyl)-4-pentyloxy-1H-pyridin-2-one
[0506] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 0.95(t, 3H),
1.31-1.44 (m, 4H), 1.73-1.79 (m, 2H), 3.91 (t, 2H), 5.08 (s, 2H),
5.60 (br s, 2H), 5.86 (d, 1H), 5.95 (dd, 1H), 7.22 (d, 1H)
EXAMPLE 152
5-chloro-6-(2-oxo-4-pentyloxy-2H-pyridin-1-ylmethyl)-3H-benzoxazole-2-one
[0507] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 0.94 (t, 3H),
1.38-1.46 (m, 4H), 1.76-2.05 (m, 2H), 3.97 (t, 2H), 5.11 (s, 2H),
6.01-6.07 (m, 2H), 6.72 (s, 1H), 6.73 (s, 1H), 7.22 (d, 1H), 9.35
(br s, 1H)
EXAMPLE 153
1-(2-chloro-4-hydroxy-benzyl)-4-pentyloxy-1H-pyridin-2-one
[0508] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 0.92 (t, 3H),
1.30-1.41 (m, 4H), 1.70-1.80 (m, 2H), 3.90 (t, 2H), 5.09 (s, 2H),
5.94-6.01 (m, 2H), 6.60 (dd, 1H), 6.88 (d, 1H), 7.00 (d, 1H), 7.28
(d, 1H), 9.75 (br s, 1H)
EXAMPLE 154
1-(2-chloro-4-isopropoxy-benzyl)-4-pentyloxy-1H-pyridin-2-one
[0509] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 0.92 (t, 3H), 1.31
(d, 6H), 1.35-1.45 (m, 4H), 1.73-1.80 (m, 2H), 3.90 (t, 2H),
4.46-4.54 (m, 1H), 5.11 (s, 2H), 5.85-5.91 (m, 2H), 6.74 (dd, 1H),
6.91 (d, 1H), 7.16 (d 1H), 7.23 (d, 1H)
EXAMPLE 155
2-[3-(2-oxo-4-pentyloxy-2H-pyridin-1-yl)-propyl]-isoindole-1,3-dione
[0510] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 0.93 (t, 3H),
1.20-1.33 (m, 4H), 1.71-1.80 (m, 2H), 2.09-2.18 (m, 2H), 3.75 (t,
2H), 3.87-3.94 (m, 4H), 5.86 (d, 1H), 5.91 (dd, 1H), 7.27 (s, 1H),
7.72-7.76 (m, 2H), 7.83-7.87 (m, 2H)
EXAMPLE 156
1-(3-amino-propyl)-4-pentyloxy-1H-pyridin-2-one
[0511] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 0.93 (t, 3H),
1.36-1.44 (m, 4H), 1.75-1.80 (m, 2H), 2.26-2.30 (m, 2H), 3.00 (t,
2H), 3.91 (t, 2H), 4.10 (t, 2H), 5.90 (d, 1H), 6.02 (d, 1H), 7.25
(d, 1H)
EXAMPLE 157
N-[3-(2-oxo-4-pentyloxy-2H-pyridin-1-yl)-propyl]-acetamide
[0512] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 0.93 (t, 3H),
1.34-1.44 (m, 4H), 1.73-1.89 (m, 4H), 2.01 (s, 3H), 3.15-3.21 (m,
2H), 3.92 (t, 2H), 3.98 (t, 2H), 5.89 (d, 1H), 5.98 (dd, 1H), 7.08
(br s, 1H), 7.14 (d, 1H)
EXAMPLE 158
1-(3-dimethylamino-propyl)-4-pentyloxy-1H-pyridin-2-one
[0513] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 0.93 (t, 3H),
1.37-1.42 (m, 4H), 1.72-1.78 (m, 4H), 2.31-2.39 (m, 2H), 3.16-3.20
(m, 2H), 3.40 (s, 6H), 3.90 (t, 2H), 4.11 (t, 2H), 5.84 (s, 1H),
5.97 (d, 1H), 7.55 (d, 1H)
EXAMPLE 159
1-(2,4-dichloro-benzyl)-6-methyl-4-pentyloxy-1H-pyridin-2-one
[0514] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 0.93 (t, 3H),
1.34-1.44 (m, 4H), 1.73-1.92 (m, 2H), 2.13 (s, 3H), 3.93 (t, 2H),
5.28 (d, 2H), 5.82 (d, 1H), 5.88 (d, 1H), 6.72 (d, 1H), 7.13 (d,
1H), 7.40 (d, 1H)
EXAMPLE 160
1-(2,4-dichloro-benzyl)-6-methyl-3-pentyl-4-pentyloxy-1H-pyridin-2-one
[0515] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 0.85-0.98 (m, 6H),
1.30-1.48 (m, 10H), 1.75-1.78 (m, 2H), 2.18 (s, 3H), 2.55 (t, 2H),
3.99 (t, 2H), 5.33 (s, 2H), 5.94 (s, 1H), 6.65 (d, 1H), 7.12 (dd,
1H), 7.39 (d, 1H)
EXAMPLE 161
1-(2-amino-ethyl)-4-pentyloxy-1H-pyridin-2-one
[0516] .sup.1H NMR (CDCl.sub.3+a few drop of CD.sub.3OD, 300 MHz)
.delta. 0.93 (t, 3H), 1.31-1.40 (m, 4H), 1.75-1.79 (m, 2H), 2.95
(t, 2H), 3.81-4.00 (m, 4H), 5.83-5.91 (m, 2H), 7.08 (d, 1H)
EXAMPLE 162
N-[2-(2-oxo-4-pentyloxy-2H-pyridin-1-yl)-ethyl]-acetamide
[0517] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 0.92 (t, 3H)
1.31-1.42 (m, 4H), 1.72-1.79 (m, 2H), 1.96 (s, 3H), 3.53 (q, 2H),
3.90 (t, 2H), 4.05 (t, 2H), 5.87 (d, 1H), 5.94 (dd, 2H), 6.89 (br
s, 1H), 7.13 (d, 1H)
EXAMPLE 163
N-[1,1-dimethyl-2-(2-oxo-4-pentyloxy-2H-pyridin-1-yl)-ethyl]-methanesulfon-
amide
[0518] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 0.93 (t, 3H),
1.29-1.46 (m, 10H), 1.75-1.80 (m, 2H), 2.98 (s, 3H), 3.92 (t, 2H),
3.99 (s, 2H), 5.91-5.97 (m, 2H), 6.56 (br s, 1H), 7.23 (d, 1H)
EXAMPLE 164
N-[1-(2-oxo-4-pentyloxy-2H-pyridin-1-ylmethyl)-propyl]-methanesulfonamide
[0519] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 0.93 (t, 3H), 1.05
(t, 3H), 1.30-1.40 (m, 4H), 1.59-1.81 (m, 4H), 2.75 (s, 3H),
3.65-4.15 (m, 6H), 5.75 (d, 1H), 5.91 (d, 1H), 5.97 (dd, 1H), 7.19
(d, 1H)
EXAMPLE 165
1-(7-nitro-benzo[1,3]dioxol-5-ylmethyl)-4-pentyloxy-1H-pyridin-2-one
[0520] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 0.95 (t, 3H),
1.32-1.42 (m, 4H), 1.75-1.82 (m, 2H), 3.95 (t, 2H), 5.42 (s, 2H),
5.94-6.00 (m, 2H), 6.09 (s, 2H), 6.55 (s, 1H), 7.18 (d, 1H), 7.63
(s, 1H)
EXAMPLE 166
1-(2-chloro-3-nitro-benzyl)-4-pentyloxy-1H-pyridin-2-one
[0521] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 0.97 (t, 3H),
1.27-1.53 (m, 4H), 1.77-1.82 (m, 2H), 3.95 (t, 2H), 5.25 (s, 2H),
5.96-6.00 (m, 2H), 7.22 (d, 1H), 7.35-7.44 (m, 2H), 7.73 (d,
1H)
EXAMPLE 167
1-(3-amino-2-chloro-benzyl)-4-pentyloxy-1H-pyridin-2-one
[0522] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 0.91 (t, 3H),
1.37-1.43 (m, 4H), 1.72-1.76 (m, 2H), 3.89 (t, 2H), 4.13 (br s),
5.12 (s, 2H), 5.86-5.92 (m, 2H), 6.47 (d, 1H), 6.70 (d, 1H),
6.96-7.07 (m, 2H)
EXAMPLE 168
N-[2-chloro-3-(2-oxo-4-pentyloxy-2H-pyridin-1-ylmethyl)-phenyl]-acetamide
[0523] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 0.94 (t, 3H),
1.27-1.44 (m, 4H), 1.74-1.81 (m, 2H), 2.26 (s, 3H), 3.93 (t, 2H),
5.19 (s, 2H), 5.90-5.94 (m, 2H), 6.87 (d, 1H), 7.06 (d, 1H), 7.23
(d, 1H), 7.69 (br s, 1H), 8.30 (d, 1H)
EXAMPLE 169
N-[2,chloro-3-(2-oxo-4-pentyloxy-2H-pyridin-1-ylmethyl)-phenyl]-methanesul-
fonamide
[0524] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 0.94 (t, 3H),
1.37-1.43 (m, 4H), 1.75-1.81 (m, 2H), 3.03 (s, 3H), 3.94 (t, 2H),
5.18 (s, 2H), 5.94-5.97 (m, 2H), 6.90 (d, 1H), 7.00 (br s, 1H),
7.12 (d, 1H), 7.28 (d, 1H), 7.60 (d, 1H)
EXAMPLE 170
N,N'-[2-chloro-3-(2-oxo-4-pentyloxy-2H-pyridin-1-ylmethyl)-phenyl]-dimetha-
nesulfonamide
[0525] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 0.94 (t, 3H),
1.26-1.41 (m, 4H), 1.76-1.81 (m, 2H), 3.49 (s, 6H), 3.94 (t, 2H),
5.23 (s, 2H), 5.94-5.96 (m, 2H), 7.15 (d, 1H), 7.25-7.38 (m,
3H)
EXAMPLE 171
1-[2-chloro-3-(2-hydroxy-ethylamino)-benzyl]-4-pentyloxy-1H-pyridin-2-one
[0526] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 0.93 (t, 3H),
1.28-1.38 (m, 4H), 1.74-1.79 (m, 2H), 2.00 (br s, 1H), 3.37 (br s,
2H), 3.89-3.94 (m, 4H), 4.74 (br s, 1H), 5.15 (s, 2H), 5.87 (dd,
1H), 5.93 (d, 1H), 6.48 (d, 1H), 6.66 (d, 1H), 7.05-7.12 (m,
2H)
EXAMPLE 172
4-chloro-2-(2-chloro-benzyl)-5-pentyloxy-2H-pyridazin-3-one
[0527] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 0.91 (t, 3H),
1.30-1.47 (m, 4H), 1.70-1.79 (m, 2H), 4.59 (t, 2H), 5.43 (s, 2H),
7.07-7.10 (m, 1H), 7.18-7.26 (m, 2H), 7.38 (dd, 1H), 7.74 (s,
1H)
EXAMPLE 173
2-(2-chloro-benzyl)-5-pentyloxy-2H-pyridazin-3-one
[0528] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 0.93 (t, 3H),
1.26-1.49 (m, 4H), 1.85-1.94 (m, 2H), 3.99 (t, 2H), 5.49 (s, 2H),
6.38 (d, 1H), 7.16-7.39 (m, 4H), 7.67 (d, 1H)
EXAMPLE 174
1-(3-amino-2,6-dichloro-benzyl)-4-pentyloxy-1H-pyridin-2-one
[0529] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 0.92 (t, 3H),
1.25-1.44 (m, 4H), 1.70-1.80 (m, 2H), 3.90 (t, 2H), 4.19 (s, 2H),
5.33 (s, 2H), 5.79 (dd, 1H), 5.92 (d, 1H), 6.74 (dd, 2H), 7.18 (d,
1H)
EXAMPLE 175
1-(3-benzyloxy-2-chloro-4-methoxy-benzyl)-4-pentyloxy-1H-pyridin-2-one
[0530] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 0.91 (t, 3H),
1.35-1.43 (m, 4H), 1.72-1.79 (m, 2H), 3.84 (s, 3H), 3.90 (t, 2H),
5.02 (s, 2H), 5.12 (s, 2H), 5.84-5.91 (m, 2H), 6.79 (d, 1H), 7.01
(d, 1H), 7.11 (d, 1H), 7.33-7.40 (m, 3H), 7.49-7.54 (m, 2H)
EXAMPLE 176
1-(2-chloro-3,4-dimethoxy-benzyl)-4-pentyloxy-1H-pyridin-2-one
[0531] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 0.94 (t, 3H),
1.27-1.41 (m, 4H), 1.74-1.80 (m, 2H), 3.86-3.94 (m, 8H), 5.13 (s,
2H), 5.87-5.92 (m, 2H), 6.80 (d, 1H), 7.03 (d, 1H), 7.18 (d,
1H)
EXAMPLE 177
1-(2-chloro-3-hydroxy-4-methoxy-benzyl)-4-pentyloxy-1H-pyridin-2-one
[0532] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 0.95 (t, 3H),
1.26-1.39 (m, 4H), 1.73-1.76 (m, 2H), 3.89-3.93 (m, 5H), 5.13 (s,
2H), 5.86-5.90 (m, 2H), 6.75 (d, 1H), 6.83 (d, 1H), 7.13 (d,
1H)
EXAMPLE 178
1-[2-chloro-4-methoxy-3-(2-methoxy-ethoxy)-benzyl]-4-pentyloxy-1H-pyridin--
2-one
[0533] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 0.92 (t, 3H),
1.26-1.39 (m, 4H), 1.74-1.82 (m, 2H), 3.45 (s, 3H), 3.74 (t, 2H),
3.84 (s, 3H), 3.91 (t, 2H), 4.15 (t, 2H), 5.12 (s, 2H), 5.86-5.91
(m, 2H), 6.78 (d, 1H), 7.00 (d, 1H), 7.15 (d, 1H)
EXAMPLE 179
1-[2-chloro-4-methoxy-3-(2-pyrrolidin-1-yl-ethoxy)-benzyl]-4-pentyloxy-1H--
pyridin-2-one
[0534] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 0.93 (t, 3H),
1.33-1.39 (m, 4H), 1.77-1.84 (m, 6H), 2.71 (m, 4H), 2.97 (t, 2H),
3.83 (s, 3H), 3.91 (t, 2H), 4.13 (t, 2H), 5.12 (s, 2H), 5.86-5.92
(m, 2H), 6.78 (d, 1H), 7.00 (d, 1H), 7.15 (d, 1H)
EXAMPLE 180
1-[2-chloro-3-(2-dimethylamino-ethoxy)-4-methoxy-benzyl]-4-pentyloxy-1H-py-
ridin-2-one
[0535] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 0.94 (t, 3H),
1.33-1.42 (m, 4H), 1.75-1.82 (m, 2H), 2.41 (s, 6H), 2.83 (t, 2H),
3.97 (t, 2H), 4.11 (t, 2H), 5.13 (s, 2H), 5.94 (s, 1H), 6.04 (dd,
1H), 6.87 (dd, 1H), 6.94 (dd, 1H), 7.27 (d, 1H)
EXAMPLE 181
2-{3-[2-chloro-6-methoxy-3-(2-oxo-4-pentyloxy-2H-pyridin-1-ylmethyl)-pheno-
xyl]-propyl}-isoindole-1,3-dione
[0536] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 0.92 (t, 3H),
1.28-1.38 (m, 4H), 1.73-1.77 (m, 2H), 3.59 (s, 3H), 3.89 (t, 2H),
4.12 (t, 2H), 4.26 (t, 2H), 5.03 (s, 2H), 5.85-5.91 (m, 2H), 6.69
(d, 1H), 6.95 (d, 1H), 7.08 (d, 1H), 7.74 (d, 2H), 7.87 (d, 2H)
EXAMPLE 182
1-[3-(2-dimethylamino-ethoxy)-2-methyl-benzyl]-4-pentyloxy-1H-pyridin-2-on-
e
[0537] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 0.94 (t, 3H),
1.26-1.35 (m, 4H), 1.75-1.79 (m, 2H), 2.15 (s, 3H), 2.37 (s, 6H),
2.79 (t, 2H), 3.93 (t, 2H), 4.09 (t, 2H), 5.08 (s, 2H), 5.83-5.94
(m, 2H), 6.70 (d, 1H), 6.83-6.92 (m, 2H), 7.15 (t, 1H), 7.28 (s,
1H)
EXAMPLE 183
1-[2-chloro-3-(2-dimethylamino-ethylamino)-benzyl]-4-pentyloxy-1H-pyridin--
2-one
[0538] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 0.93 (t, 3H),
1.30-1.40 (m, 4H), 1.55-1.59 (m, 2H), 2.29 (s, 6H), 2.62 (t, 2H),
3.20 (t, 2H), 3.92 (t, 2H), 5.00 (br s, 1H), 5.16 (s, 2H),
5.86-5.93 (m, 2H), 6.47 (d, 1H), 6.61 (d, 1H), 7.06-7.13 (m,
2H)
EXAMPLE 184
1-[2,6-dichloro-3-(2-hydroxy-ethylamino)-benzyl]-4-pentyloxy-1H-pyridin-2--
one
[0539] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 0.91 (t, 3H),
1.32-1.42 (m, 4H), 1.72-1.79 (m, 2H), 2.54 (t, 1H), 3.36 (q, 2H),
3.87-3.94 (m, 4H), 4.84 (t, 1H), 5.27 (s, 2H), 5.78 (dd, 1H), 5.91
(d, 1H), 6.68-6.71 (m, 2H), 7.23 (d, 1H)
EXAMPLE 185
1-[2,6-dichloro-3-(2-dimethylamino-ethylamino)-benzyl]-4-pentyloxy-1H-pyri-
din-2-one
[0540] .sup.1H NMR (CD.sub.3OD, 300 MHz) .delta. 0.93 (t 3H),
1.38-1.46 (m, 4H), 1.75-1.80 (m, 2H), 2.55 (s, 6H), 2.91 (t, 2H),
3.46 (t, 2H), 3.99 (t, 2H), 5.32 (s, 2H), 5.96 (d, 1H), 6.02 (dd,
1H), 6.88 (d, 1H), 6.93 (d, 1H), 7.35 (d, 1H)
EXAMPLE 186
1-[2,6-dichloro-3-(3-hydroxy-propylamino)-benzyl]-4-pentyloxy-1H-pyridin-2-
-one
[0541] .sup.1H NMR (CD.sub.3OD, 300 MHz) .delta. 0.93 (t, 3H),
1.38-1.45 (m, 4H), 1.75-1.90 (m, 4H), 3.48-3.53 (m, 2H), 3.69 (t,
2H), 3.98 (t, 2H), 5.31 (s, 2H), 5.95 (d, 1H), 6.01 (dd, 1H), 6.83
(d, 1H), 6.90 (d, 1H), 7.30 (d, 1H)
EXAMPLE 187
1-[2,6-dichloro-3-(3-dimethylamino-propylamino)-benzyl]-4-pentyloxy-1H-pyr-
idin-2-one
[0542] .sup.1H NMR (CDCl.sub.3+a few drop of CD.sub.3OD, 300 MHz)
.delta. 0.79 (t, 3H), 1.13-1.30 (m, 4H), 1.61-1.77 (m, 4H), 2.20
(s, 6H), 2.38 (t, 2H), 3.11 (t, 2H), 3.80 (t, 2H), 5.18 (s, 2H),
5.76 (dd, 1H), 5.81 (d, 1H), 6.54 (d, 1H), 6.64 (d, 1H), 7.13 (d,
1H)
EXAMPLE 188
1-[3-(3-amino-propylamino)-2,6-dichloro-benzyl]-4-pentyloxy-1H-pyridin-2-o-
ne
[0543] .sup.1H NMR (CD.sub.3OD, 300 MHz) .delta. 0.94 (t, 3H),
1.38-1.46 (m, 4H), 1.75-1.80 (m, 2H), 1.94-2.01 (m, 2H), 3.01-3.06
(m, 2H), 3.32-3.39 (m, 2H), 3.99 (t, 2H), 5.31 (s, 2H), 5.95 (d,
1H), 6.02 (dd, 1H), 6.87 (d, 1H), 6.92 (d, 1H), 7.33 (d, 1H)
EXAMPLE 189
1-(3-fluoro-2-methyl-benzyl)-4-pentyloxy-1H-pyridin-2-one
[0544] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 0.93 (t, 3H),
1.32-1.46 (m, 4H), 1.75-1.78 (m, 2H), 2.19 (s, 3H), 3.93 (t, 2H),
5.08 (s, 2H), 5.86-5.94 (m, 2H), 6.82 (d, 1H), 6.92-7.02 (m, 2H),
7.10-7.15 (m, 1H)
EXAMPLE 190
1-(2-chloro-3-dimethylaminomethyl-4-fluoro-benzyl)-4-pentyloxy-1H-pyridin--
2-one
[0545] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 0.92 (t, 3H),
1.33-1.45 (m, 4H), 1.72-1.86 (m, 2H), 3.55 (s, 6H), 3.91 (t, 2H),
4.91 (s, 2H), 5.19 (s, 2H), 5.88 (d, 1H), 5.98 (dd, 1H), 7.12-7.42
(m, 3H)
EXAMPLE 191
1-(2,6-dichloro-3-methylamino-benzyl)-4-pentyloxy-1H-pyridin-2-one
[0546] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 0.92 (t, 3H),
1.32-1.42 (m, 4H), 1.75-1.79 (m, 2H), 2.91 (d, 3H), 3.90 (t, 2H),
4.49 (q, 1H), 5.33 (s, 2H), 5.78 (dd, 1H), 5.92 (d, 1H), 6.63 (d,
1H), 6.70 (d, 1H), 7.28 (d, 1H)
EXAMPLE 192
1-(2,6-dichloro-3-dimethylamino-benzyl)-4-pentyloxy-1H-pyridin-2-one
[0547] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 0.92 (t, 3H),
1.34-1.41 (m, 4H), 1.72-1.78 (m, 2H), 2.80 (s, 6H), 3.90 (t, 2H),
5.38 (s, 2H), 5.79 (dd, 1H), 5.93 (d, 1H), 6.69 (d, 1H), 7.08 (d,
1H), 7.33 (d, 1H)
EXAMPLE 193
[2-chloro-3-(2-oxo-4-pentyloxy-2H-pyridin-1-ylmethyl)-phenylamino]-acetic
acid
[0548] .sup.1H NMR (DMSO-d.sub.6, 300 MHz) .delta. 0.89 (t, 3H),
1.32-1.37 (m, 4H), 1.67-1.71 (m, 2H), 3.90-3.97 (m, 4H), 5.03 (s,
2H), 5.69 (br s, 1H), 5.83 (s, 1H), 5.99 (d, 1H), 6.05 (d, 1H),
6.52 (d, 1H), 7.05 (t, 1H), 7.51 (d, 1H)
EXAMPLE 194
1-(6-chloro-benzo[1,3]dioxol-5-ylmethyl)-4-(pyridin-4-ylmethoxy)-1H-pyridi-
n-2-one
[0549] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 5.02 (s, 2H), 5.09
(s, 2H), 5.95-6.01 (m, 4H), 6.84 (d, 1H) 7.21-7.31 (m, 4H), 8.62
(d, 2H)
EXAMPLE 195
1-(6-chloro-benzo[1,3]dioxol-5-ylmethyl)-4-(6-chloro-pyridin-3-ylmethoxy)--
1H-pyridin-2-one
[0550] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 4.98 (s, 2H), 5.09
(s, 2H), 5.92-5.99 (m, 4H), 6.83 (d, 1H), 7.22-7.40 (m, 3H), 7.70
(dd, 1H), 8.40 (dd, 1H)
EXAMPLE 196
1-(6-chloro-benzo[1,3]dioxol-5-ylmethyl)-4-(4-methoxy-3,5-dimethylpyridin--
2-ylmethoxy)-1H-pyridin-2-one
[0551] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 2.27 (s, 6H), 3.78
(s, 3H), 5.09 (s, 4H), 6.09-6.10 (m, 4H), 6.84 (s, 2H), 7.17 (s,
1H), 7.21 (s, 1H), 8.25 (s, 1H)
EXAMPLE 197
1-(6-chloro-benzo[1,3]dioxol-5-ylmethyl)-4-(2-methyl-pyridin-3-ylmethoxy)--
1H-pyridin-2-one
[0552] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 2.58 (s, 3H), 5.00
(s, 2H), 5.13 (s, 2H), 5.96-5.98 (m, 3H), 6.05 (d, 1H), 6.87 (d,
2H), 7.19 (dd, 1H), 7.25-7.29 (m, 1H), 7.67 (d, 1H), 8.51 (d,
1H)
EXAMPLE 198
1-(6-chloro-benzo[1,3]dioxol-5-ylmethyl)-4-(thiazol-4-ylmethoxy)-1H-pyridi-
n-2-one
[0553] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 5.12 (s, 2H), 5.21
(s, 2H), 5.98 (s, 2H) 6.01 (dd, 1H), 6.07 (d, 1H), 6.86 (d, 2H),
7.24 (d, 1H), 7.43 (s, 1H), 8.87 (s, 1H)
EXAMPLE 199
1-(6-chloro-benzo[1,3]dioxol-5-ylmethyl)-4-(pyridin-2-ylmethoxy)-1H-pyridi-
n-2-one
[0554] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 5.12 (s, 2H) 5.16
(s, 2H), 5.98 (s, 2H), 6.03-6.05 (m, 2H), 6.86 (d, 2H), 7.25-7.29
(m, 2H), 7.45 (d, 1H), 7.75 (td, 1H), 8.63 (d, 1H)
EXAMPLE 200
pentanoic acid
1-(6-chloro-benzo[1,3]dioxol-5-ylmethyl)-2-oxo-1,2-dihydro-pyridin-4-yl
ester
[0555] H NMR (CDCl.sub.3, 300 MHz) .delta. 0.97 (t 3H), 1.39-1.47
(m, 2H), 1.68-1.75 (m, 2H), 2.54 (t, 2H), 5.15 (s, 2H), 5.98 (s,
2H), 6.09 (dd, 1H), 6.38 (d, 1H), 6.86 (s, 1H), 6.91 (s, 1H), 7.37
(d, 1H)
EXAMPLE 201
hexanoic acid
1-(6-chloro-benzo[1,3]dioxol-5-ylmethyl)-2-oxo-1,2-dihydro-pyridin-4-yl
ester
[0556] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 0.93 (t, 3H),
1.34-1.38 (m, 4H), 1.70-1.76 (m, 2H), 2.54 (t, 2H), 5.16 (s, 2H),
5.98 (s, 2H), 6.10 (dd, 1H), 6.40 (d, 1H), 6.87 (s, 1H), 6.91 (s,
1H), 7.37 (d, 1H)
EXAMPLE 202
1-(2-chloro-3-trifluoromethyl-benzyl)-4-pentyloxy-1H-pyridin-2-one
[0557] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 0.95 (t, 3H),
1.37-1.45 (m, 4H), 1.78-1.81 (m, 2H), 3.94 (t, 2H), 5.25 (s, 2H),
5.95-5.98 (m, 2H), 7.19-7.38 (m, 3H), 7.65 (d, 1H)
EXAMPLE 203
thiophene-2-carboxyl acid
1-(6-chloro-benzo[1,3]dioxol-5-ylmethyl)-2-oxo-1,2-dihydro-pyridin-4-yl
ester
[0558] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 5.19 (s, 2H), 6.00
(s, 2H), 6.24 (dd, 1H), 6.53 (d, 1H), 6.88 (s, 1H), 6.94 (s, 1H),
7.21 (t, 1H), 7.42 (d, 1H), 7.72 (d, 1H), 7.98 (d, 1H)
EXAMPLE 204
toluene-4-sulfonic acid
1-(6-chloro-benzo[1,3]dioxol-5-ylmethyl)-2-oxo-1,2-dihydro-pyridin-4-yl
ester
[0559] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 2.48 (s, 3H) 5.10
(s, 2H), 6.00 (s, 2H), 6.14-6.15 (m, 2H), 6.84 (s, 1H), 6.87 (s,
1H), 7.34-7.35 (m, 1H), 7.38 (d, 2H), 7.81 (d, 2H)
EXAMPLE 205
1-(6-chloro-benzo[1,3]dioxol-5-ylmethyl)-4-(4,4,5,5,5-pentafluoro-pentylox-
y)-1H-pyridin-2-one
[0560] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 2.08-2.28 (m, 4H),
4.01 (t, 2H), 5.12 (s, 2H), 5.91-5.93 (m, 2H), 5.98 (s, 2H), 6.84
(s, 1H), 6.87 (s, 1H), 7.22-7.24 (m, 1H)
EXAMPLE 206
1-(6-chloro-benzo[1,3]dioxol-5-ylmethyl)-4-(2-dimethylamino-ethoxy)-1H-pyr-
idin-2-one
[0561] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 2.33 (s, 6H), 2.73
(t, 2H), 4.03 (t, 2H), 5.11 (s, 2H), 5.94-5.97 (m, 4H), 6.83 (s,
1H), 6.86 (s, 1H), 7.19 (d, 1H)
EXAMPLE 207
4-chloro-2-(2,4-dichloro-benzyloxy)-pyridine
[0562] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 5.17 (s, 2H), 6.83
(dd, 1H), 6.93 (d, 1H), 7.28-7.47 (m, 3H), 8.23 (d, 1H)
EXAMPLE 208
4-chloro-1-(2,4-dichloro-benzyl)-1H-pyridin-2-one
[0563] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 5.17 (s, 2H), 6.21
(dd, 1H), 6.65 (s, 1H), 7.22-7.42 (m, 3H), 7.43 (s, 1H)
EXAMPLE 209
1-(2,4-dichloro-benzyl)-4-(5-fluoro-pentyloxy)-1H-pyridin-2-one
[0564] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 1.58-1.61 (m, 2H),
1.74-1.88 (m, 4H), 3.96 (t, 2H), 4.44 (t, 1H), 4.54 (t, 1H), 5.16
(s, 2H), 5.93-5.94 (m, 2H), 7.18-7.22 (m, 3H), 7.42 (s, 1H)
EXAMPLE 210
3-[1-(2,4-dichloro-benzyl)-2-oxo-1,2-dihydro-pyridin-4-yloxymethyl]-indole-
-1-carboxyl acid tetra-butyl ester
[0565] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 1.61 (s, 9H), 5.18
(s, 2H), 5.40 (s, 2H), 5.95 (dd, 1H), 6.15 (d, 1H), 7.21-7.60 (m,
7H), 8.23 (d, 1H)
EXAMPLE 211
1-(2,4-dichloro-benzyl)-4-(2-thiophen-2-yl-ethoxy)-1H-pyridin-2-one
[0566] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 3.30 (t, 2H), 4.15
(t, 2H) 5.13 (s, 2H), 5.90-5.97 (m, 2H), 6.87-6.98 (m, 2H),
7.15-7.22 (m, 4H), 7.41 (s, 1H)
EXAMPLE 212
1-(2,4-dichloro-benzyl)-4-(2-thiophen-3-yl-ethoxy)-1H-pyridin-2-one
[0567] .sup.1H NMR (CDCl.sub.3, 300 MHz) 63.12 (t, 2H), 4.15 (t,
2H) 5.12 (s, 2H), 5.88-5.97 (m, 2H), 6.95-7.41 (m, 7H)
EXAMPLE 213
1-(2,4-dichloro-benzyl)-4-(2-pyrrol-1-yl-ethoxy)-1H-pyridin-2-one
[0568] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 4.18 (t, 2H), 4.28
(t, 2H), 5.14 (s, 2H), 5.82-5.97 (m, 2H), 6.70-6.80 (m, 2H),
7.10-7.25 (m, 3H), 7.40 (s, 1H)
EXAMPLE 214
1-(2,4-dichloro-benzyl)-4-(3-pyrrol-1-yl-propoxy)-1H-pyridin-2-one
[0569] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 2.20 (m, 2H), 3.82
(t, 2H), 4.03 (t, 2H), 5.14 (s, 2H), 5.86 (d, 1H), 5.94 (dd, 1H),
6.12-6.18 (m, 2H), 6.60-6.66 (m, 2H), 7.18-7.24 (m, 3H), 7.40 (s,
1H)
EXAMPLE 215
1-(3-amino-2-methyl-benzyl)-4-(2-thiophen-2-yl-ethoxy)-1H-pyridin-2-one
[0570] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 2.01 (s, 3H), 3.28
(t, 2H), 3.65 (br s, 2H), 4.14 (t, 2H), 5.04 (s, 2H), 5.84 (dd,
1H), 5.95 (d, 1H), 6.57 (d, 1H), 6.70 (d, 1H), 6.88-7.02 (m, 4H),
7.16 (dd, 1H)
EXAMPLE 216
1-(3-amino-2-methyl-benzyl)-4-(2-pyrrol-1-yl-ethoxy)-1H-pyridin-2-one
[0571] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 2.01 (s, 3H), 4.16
(t, 2H), 4.25 (t, 2H), 5.04 (s, 2H), 5.83 (dd, 1H), 5.90 (d, 1H),
6.16 (t, 2H), 6.57 (d, 1H), 6.71-6.75 (m, 3H), 6.91 (d, 1H), 7.02
(t, 1H)
EXAMPLE 217
1-(3-amino-2-methyl-benzyl)-4-[2-(4-methyl-thiazol-5-yl)-ethoxy]-1H-pyridi-
n-2-one
[0572] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 1.98 (s, 3H), 2.40
(s, 3H), 3.20 (t, 2H), 3.46 (br s, 2H), 4.06 (t, 2H), 5.02 (s, 2H),
5.81 (dd, 1H), 5.92 (d, 1H), 6.53 (d, 1H), 6.68 (d, 1H), 6.91 (d,
1H), 6.99 (t, 1H), 8.56 (s, 1H)
EXAMPLE 218
1-(3-Amino-2-methyl-benzyl)-4-(2-(5-bromothiophen-2-yl)-ethoxy)-1H-pyridin-
-2-one
[0573] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 1.95 (s, 3H), 3.14
(t, 2H), 3.49 (br s, 2H), 4.05 (t, 2H), 4.99 (s, 2H), 5.81 (dd,
1H), 5.88 (m, 1H), 6.49 (d, 1H), 6.60 (m, 1H), 6.64 (d, 1H), 6.83
(m, 1H), 6.89 (dd, 1H), 6.96 (t, 1H)
EXAMPLE 219
1-(3-Amino-2-methyl-benzyl)-4-(2-(5-fluorothiophen-2-yl)-ethoxy)-1H-pyridi-
n-2-one
[0574] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 2.02 (s, 3H), 3.12
(dt, 2H), 4.09 (t, 2H), 5.05 (s, 2H), 5.85 (dd, 1H), 5.93 (d, 1H),
6.28 (dd, 1H), 6.46 (d, 1H), 6.58 (d, 1H), 6.72 (d, 1H), 6.92 (d,
1H), 7.03 (t, 1H)
EXAMPLE 220
1-[3-(2-Hydroxy-ethylamino)-2-methyl-benzyl]-4-(2-thiophen-2-yl-ethoxy)-1H-
-pyridin-2-one
[0575] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 1.96 (s, 3H), 3.29
(m, 4H), 3.88 (t, 2H), 4.12 (t, 2H), 5.02 (s, 2H), 5.84 (dd, 1H),
5.93 (d, 1H), 6.53 (d, 1H), 6.66 (d, 1H), 6.92 (m, 3H), 7.10 (t,
1H), 7.16 (dd, 1H)
EXAMPLE 221
2-{2-Methyl-3-[2-oxo-4-(2-thiophene-2-yl-ethoxy)-2H-pyridin-1-ylmethyl]-ph-
enylamino}-acetamide
[0576] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 2.01 (s, 3H), 3.22
(t, 2H), 3.60 (d, 2H), 4.17 (t, 2H), 4.97 (s, 2H), 5.86 (m, 1H),
5.94 (dd, 1H), 6.20 (d, 1H), 6.29 (d, 1H), 6.95 (m, 3H), 7.33 (m,
2H)
EXAMPLE 222
1-[3-(Cyclopropylmethyl-amino)-2-methyl-benzyl]-4-(2-thiophen-2-yl-ethoxy)-
-1H-pyridin-2-one
[0577] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 0.25 (dt, 2H),
0.57 (dt, 2H), 1.06-1.19 (m, 1H), 2.01 (s, 3H), 2.98 (d, 2H), 3.27
(t, 2H), 3.73 (br s, 1H), 4.14 (t, 2H), 5.05 (s, 2H), 5.82 (dd,
1H), 5.94 (d, 1H), 6.87-6.95 (m, 3H), 7.10 (t, 1H)
EXAMPLE 223
N-{2-Methyl-3-[2-oxo-4-(2-thiophen-2-yl-ethoxy)-2H-pyridin-1-ylmethyl]-phe-
nylamino}-acetonitrile
[0578] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 2.00 (s, 3H), 3.28
(t, 2H), 4.14 (m, 4H), 5.07 (s, 2H), 5.87 (dd, 1H), 5.93 (d, 1H),
6.66 (d, 1H), 6.71 (d, 1H), 6.93-6.96 (m, 3H), 7.15-7.19 (m,
2H)
EXAMPLE 224
N-(2-{2-Methyl-3-[2-oxo-4-(2-thiophen-2-yl-ethoxy)-2H-pyridin-1-ylmethyl]--
phenylamino}-ethyl)-acetamide
[0579] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 1.99 (m, 6H),
3.26-3.32 (m, 4H), 3.53-3.59 (m, 2H), 4.14 (t, 2H), 5.05 (s, 2H),
5.82 (dd, 1H), 5.94 (d, 1H), 6.52 (d, 1H), 6.61(d, 1H), 6.89-6.69
(m, 3H), 7.10 (t, 1H), 7.15 (d, 1H)
EXAMPLE 225
1-[2-Methyl-3-(2-pyrrol-1-yl-ethylamino)-benzyl]-4-(2-thiophen-2-yl-ethoxy-
)-1H-pyridin-2-one
[0580] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 1.85 (s, 3H), 3.28
(t, 2H), 3.51 (t, 3H), 4.14 (t, 4H), 5.05 (s, 2H), 5.84 (dd, 1H),
5.93 (d, 1H), 6.17 (m, 2H), 6.56 (d, 1H), 6.65 (m, 3H), 6.90 (m,
3H), 7.10-7.17 (m, 2H)
EXAMPLE 226
Synthesis of
1-[2-Methyl-3-(2-oxo-2-pyrrolidin-1-yl-ethylamino)-benzyl]-4-(2-thiophen--
2-yl-ethoxy)-1H-pyridin-2-one
[0581] A mixture of
{2-Methyl-3-[2-oxo-4-(2-thiophen-2-yl-ethoxy)-2H-pyridin-1-ylmethyl]-phen-
ylamino}-acetic acid (50 mg, 0.13 mmol), TBTU (60 mg, 0.19 mmol),
pyrrolidine (0.02 ml, 0.25 mmol) and triethylamine (0.09 ml, 0.63
mmol) was dissolved in N,N-dimethylformamide (0.5 ml) and stirred
at room temperature. After 1 hour, the resulting solution was
evaporated, extracted with dichloromethane (20 ml) and subjected to
silica gel column chromatography (ethyl acetate/MeOH, 20:1) to
obtain the titled compound (41 mg, 71%).
[0582] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 1.88-1.95 (m, 2H),
1.99-2.09 (m, 5H), 3.27 (t, 2H), 3.44 (t, 2H), 3.55 (t, 2H), 3.81
(s, 2H), 4.14 (t, 2H), 5.06 (s, 2H), 5.83 (dd, 1H), 5.95 (d, 1H),
6.51 (d, 1H), 6.54 (d, 1H), 6.87-6.94 (m, 3H), 7.10 (t, 1H) 7.16
(dd, 1H)
EXAMPLES 227 TO 230
[0583] The procedure of Example 226 was repeated except the
starting material to obtain the titled compound.
EXAMPLE 227
1-[2-Methyl-3-(2-oxo-2-piperidin-1-yl-ethylamino)-benzyl]-4-(2-thiophen-2--
yl-ethoxy)-1H-pyridin-2-one
[0584] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 1.53-1.74 (m, 6H),
2.07 (s, 3H), 3.27 (t, 2H), 3.39 (t, 2H), 3.62 (t, 2H), 3.88 (s,
2H), 4.14 (t, 2H), 5.06 (s, 2H), 5.83 (dd, 1H), 5.95 (d, 1H), 6.52
(d, 1H), 6.84-6.96 (m, 3H), 7.10 (t, 1H) 7.16 (dd, 1H)
EXAMPLE 228
N,N-Dimethyl-2-{2-methyl-3-[2-oxo-4-(2-thiophen-2-yl-ethoxy)-2H-pyridin-1--
ylmethyl]-phenylamino}-acetamide
[0585] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 2.08 (s, 3H), 3.05
(s, 6H), 3.28 (t, 2H), 3.88 (s, 2H), 4.15 (t, 2H), 5.07 (s, 2H),
5.83 (dd, 1H), 5.94 (d, 1H), 6.50-6.55 (m, 2H), 6.89-6.96 (m, 3H),
7.08-7.17 (m, 2H)
EXAMPLE 229
1-{2-Methyl-3-[2-(4-methyl-piperazin-1-yl)-2-oxo-ethylamino]-benzyl}-4-(2--
thiophen-2-yl-ethoxy)-1H-pyridin-2-one
[0586] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 2.07 (s, 3H), 2.33
(s, 3H), 2.45 (d, 4H), 3.28 (t, 2H), 3.48 (d, 2H), 3.70 (d, 2H),
3.89 (s, 2H), 4.14 (t, 2H), 5.06 (s, 2H), 5.83 (dd, 1H), 5.94 (d,
1H), 6.52 (dd, 2H), 6.88-6.97 (m, 3H), 7.08-7.17 (m, 2H)
EXAMPLE 230
1-[2-Methyl-3-(2-morpholin-4-yl-2-oxo-ethylamino)-benzyl]-4-(2-thiophen-2--
yl-ethoxy)-1H-pyridin-2-one
[0587] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 2.08 (s, 3H), 2.28
(t, 2H), 3.48 (t, 2H), 3.62-3.79 (m, 6H), 3.90 (s, 2H), 4.15 (t,
2H), 5.07 (s, 2H), 5.83 (dd, 1H), 5.94 (d, 1H), 6.48 (d, 1H), 6.54
(d, 1H), 6.88-6.96 (m, 3H), 7.08-7.18 (m, 2H)
EXAMPLES 231 TO 266
[0588] The procedure of Example 1 was repeated except the starting
material to obtain the titled compound.
EXAMPLE 231
1-(3-Amino-2-methyl-benzyl)-4-(2-furan-2-yl-ethoxy)-1H-pyridin-2-one
[0589] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 2.01 (s, 3H), 3.10
(t, 2H), 4.17 (t, 2H), 5.05 (s, 2H), 5.81 (dd, 1H), 5.95 (d, 1H),
6.10 (d, 1H), 6.30 (d, 1H), 6.57 (d, 1H), 6.69 (d, 1H), 6.90 (d,
1H), 7.02(t, 1H), 7.29 (d, 1H)
EXAMPLE 232
1-(3-Amino-2-methyl-benzyl)-4-[2-(5-methyl-thiophen-2-yl)-ethoxy]-1H-pyrid-
in-2-one
[0590] .sup.1H NMR (CD.sub.3OD, 300 MHz) .delta. 2.02(s, 3H), 2.40
(s, 3H), 3.19 (t, 2H), 4.16 (t, 2H), 5.07(s, 2H), 5.96 (d, 1H),
6.06 (dd, 1H), 6.40 (d, 1H), 6.57 (dd, 1H), 6.67 (d, 1H), 6.73 (d,
1H), 6.95 (t, 1H), 7.21 (d, 1H)
EXAMPLE 233
1-(3-Amino-2-methyl-benzyl)-4-[2-(5-chloro-thiophen-2-yl)-ethoxy]-1H-pyrid-
in-2-one
[0591] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 2.01(s, 3H), 3.18
(t, 2H), 3.70 (br s, 2H), 4.10 (t, 2H), 5.05 (s, 2H), 5.84 (dd,
1H), 2.92 (d, 1H), 6.57 (d, 1H), 6.65 (d, 1H), 6.69 (d, 1H), 6.74
(d, 1H), 6.92 (d, 1H), 7.02 (t, 1H)
EXAMPLE 234
1-(2,4-dichloro-benzyl)-4-[2-(3-methyl-thiophen-2-yl)-ethoxy]-1H-pyridin-2-
-one
[0592] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 2.20(s, 3H), 3.20
(t, 2H), 4.10 (t, 2H), 5.14 (s, 2H), 5.93-5.97 (m, 2H), 6.80 (d,
1H), 7.07 (d, 1H), 7.17-7.20 (m, 3H), 7.40 (s, 1H)
EXAMPLE 235
1-(3-Amino-2-methyl-benzyl)-4-(2-benzo[b]thiophen-3-yl-ethoxy)-1H-pyridin--
2-one
[0593] .sup.1H NMR (CD.sub.3OD, 300 MHz) .delta. 2.00 (s, 3H), 3.31
(t, 2H), 4.31 (t, 2H), 5.04 (s, 2H), 5.96-6.01 (m, 2H), 6.37 (d,
1H), 6.72 (d, 1H), 6.93 (t, 1H), 7.14-7.42 (m, 5H), 7.84 (t,
1H)
EXAMPLE 236
1-(3-Amino-2-methyl-benzyl)-4-[2-(5-chloro-3-methyl-benzo[b]thiophen-2-yl)-
-ethoxy]-1H-pyridin-2-one
[0594] .sup.1H NMR (CD.sub.3OD+a few drop of CDCl.sub.3, 300 MHz)
.delta. 1.97 (s, 3H), 2.32 (s, 3H), 3.32 (t, 2H), 4.20 (t, 2H),
5.01 (s, 2H), 5.92-5.97 (m, 2H), 6.45 (d, 1H), 6.71 (d, 1H), 6.96
(t, 1H), 7.02 (d, 1H), 7.21 (dd, 1H), 7.55 (d, 1H), 7.65 (d,
1H)
EXAMPLE 237
1-(3-amino-2-methyl-benzyl)-4-[2-(3-methyl-benzo[b]thiophen-2-yl)-ethoxy]--
1H-pyridin-2-one
[0595] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 2.00(s, 3H), 2.36
(s, 3H), 3.33 (t, 2H), 3.73 (br s, 2H), 4.18 (t, 2H), 5.05 (s, 2H),
5.82 (dd, 1H), 5.95 (d, 1H), 6.56 (d, 1H), 6.69 (d, 1H), 6.91 (d,
1H), 7.02 (t, 1H), 7.27-7.39 (m, 2H), 7.63 (d, 1H), 7.77 (d,
1H)
EXAMPLE 238
1-(3-Amino-2-methyl-benzyl)-4-[2-(5-methyl-furan-2-yl)-ethoxy]-1H-pyridin--
2-one
[0596] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 2.00 (s, 3H), 2.24
(s, 3H), 3.03 (t, 2H), 4.13 (t, 2H), 5.03 (s, 2H), 5.80-5.86 (m,
2H), 5.94-5.96 (m, 2H), 6.53 (d, 1H), 6.66 (d, 1H), 6.89 (d, 1H),
7.00(t, 1H)
EXAMPLE 239
1-(3-Amino-2-methyl-benzyl)-4-[2-(5-ethyl-furan-2-yl)-ethoxy]-1H-pyridin-2-
-one
[0597] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 1.20 (t, 3H), 1.99
(s, 3H), 2.59 (q, 2H), 3.04 (t, 2H), 3.68 (br s, 2H), 4.14 (t, 2H),
5.04 (s, 2H), 5.80 (dd, 1H), 5.86 (d, 1H), 5.94 (d, 1H), 5.97 (d,
1H), 6.55 (d, 1H), 6.67 (d, 1H), 6.89 (d, 1H), 7.00 (t, 1H)
EXAMPLE 240
5-[1-(3-amino-2-methyl-benzyl)-2-oxo-1,2-dihydro-pyridin-4-yloxymethyl]-fu-
ran-2-carboxylic acid ethyl ester
[0598] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 1.37 (t, 3H), 2.00
(s, 3H), 4.36 (q, 2H), 4.97 (s, 2H), 5.05 (s, 2H), 5.84 (dd, 1H),
6.01 (d, 1H), 6.55-6.58 (m, 2H), 6.69 (d, 1H), 6.93 (d, 1H), 7.02
(t, 1H), 7.14 (d, 1H)
EXAMPLE 241
1-[3-(2-dimethylamino-ethylamino)-2-methyl-benzyl]-4-(2-thiophen-2-yl-etho-
xy)-1H-pyridin-2-one
[0599] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 1.99 (s, 3H), 2.30
(s, 6H), 2.60 (t, 2H), 3.17 (t, 2H), 3.28 (t, 2H), 4.14 (t, 2H),
5.06 (s, 2H), 5.83 (dd, 1H), 5.94 (d, 1H), 6.88-6.96 (m, 3H),
7.09-7.18 (m, 2H)
EXAMPLE 242
1-(3-amino-2-methyl-benzyl)-4-[2-(5-methylsulfanyl-thiophen-2-yl)-ethoxy]--
1H-pyridin-2-one
[0600] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 2.01 (s, 3H), 2.45
(s, 3H), 3.21 (t, 2H), 3.70 (br s, 2H), 4.12 (t, 2H), 5.05 (s, 2H),
5.84 (dd, 1H), 5.93 (d, 1H), 6.57 (d, 1H), 6.69-6.73 (m, 2H),
6.91-6.93 (m, 2H), 7.02 (t, 1H)
EXAMPLE 243
1-(3-amino-2-methyl-benzyl)-4-(2-benzofuran-2-yl-ethoxy)-1H-pyridin-2-one
[0601] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 2.05 (s, 3H), 3.25
(t, 2H), 4.29 (t, 2H), 5.05 (s, 2H), 5.82 (d, 1H), 6.00 (s, 1H),
6.51-6.71 (m, 3H), 6.91 (d, 1H), 7.04 (t, 1H), 7.17-7.28 (m, 2H),
7.42 (d, 1H), 7.50 (d, 1H)
EXAMPLE 244
1-(3-amino-2-methyl-benzyl)-4-[2-(3-methyl-isoxazol-5-yl)-ethoxy]-1H-pyrid-
in-2-one
[0602] .sup.1H NMR (CDCl.sub.3+a few drop of CD.sub.3OD, 300 MHz)
.delta. 1.86 (s, 3H), 1.93 (s, 3H), 2.63 (t, 2H), 4.14 (t, 2H),
4.96 (s, 2H), 5.82 (dd, 1H), 5.90 (d, 1H), 6.46 (d, 1H), 6.64 (d,
1H), 6.86 (d, 1H), 6.94 (t, 1H), 7.26 (s, 1H)
EXAMPLE 245
1-(3-amino-2-methyl-benzyl)-4-[2-(4,5-dimethyl-thiophen-2-yl)-ethoxy]-1H-p-
yridin-2-one
[0603] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 2.00 (s, 3H), 2.07
(s, 3H), 2.78 (s, 3H), 3.14 (t, 2H), 4.09 (t, 2H), 5.05 (s, 2H),
5.85 (dd, 1H), 5.95 (d, 1H), 6.55 (s, 1H), 6.56 (d, 1H), 6.69 (d,
1H), 6.91 (d, 1H), 7.01 (t, 1H)
EXAMPLE 246
1-(3-amino-2-methyl-benzyl)-4-[2-(5-ethyl-thiophen-2-yl)-ethoxy]-1H-pyridi-
n-2-one
[0604] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 1.28 (t, 3H), 2.00
(s, 3H), 2.78 (q, 2H), 3.20 (t, 2H), 3.69 (br s, 2H), 4.11 (t, 2H),
5.04 (s, 2H), 5.84 (dd, 1H), 5.94 (d, 1H), 6.55-6.70 (m, 4H), 6.91
(d, 1H), 7.01 (t, 1H)
EXAMPLE 247
1-(3-amino-2,6-dichloro-benzyl)-4-(2-thiophen-2-yl-ethoxy)-1H-pyridin-2-on-
e
[0605] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 3.25 (t, 2H), 4.12
(t, 2H), 4.30 (br s, 2H), 5.30 (s, 2H), 5.81 (dd, 1H), 5.92 (d,
1H), 6.70-6.93 (m, 4H), 7.13-7.16 (m, 2H)
EXAMPLE 248
N-{2-methyl-3-[2-oxo-4-(2-thiophen-2-yl-ethoxy)-2H-pyridin-1-ylmethyl]-phe-
nyl}-acetamide
[0606] .sup.1H NMR (DMSO-d.sub.6, 300 MHz) .delta. 2.02 (s, 3H),
2.08 (s, 3H), 3.22 (t, 2H), 4.17 (t, 2H), 5.00 (s, 2H), 5.87 (d,
1H), 5.99 (dd, 1H), 6.57 (d, 1H), 6.94-6.96 (m, 2H), 7.07 (t, 1H),
7.19 (d, 1H), 7.32-7.34 (m, 1H), 7.43 (d, 1H)
EXAMPLE 249
1-[2-methyl-3-(2-piperidin-1-yl-ethylamino)-benzyl]-4-(2-thiophen-2-yl-eth-
oxy)-1H-pyridin-2-one
[0607] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 1.59 (br s, 2H),
1.83-1.87 (m, 4H), 2.07 (s, 3H), 2.90-2.94 (m, 4H), 3.06 (t, 2H),
3.28 (t, 2H), 3.52 (t, 2H), 4.13 (t, 2H), 4.60 (br s, 1H), 5.03 (s,
2H), 5.86 (dd, 1H), 5.92 (d, 1H), 6.46 (d, 1H), 6.59 (d, 1H),
6.88-6.96 (m, 3H), 7.07 (t, 1H), 7.16 (dd, 1H)
EXAMPLE 250
1-[2-methyl-3-(2-morpholin-4-yl-ethylamino)-benzyl]-4-(2-thiophen-2-yl-eth-
oxy)-1H-pyridin-2-one
[0608] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 2.00 (s, 3H), 2.47
(t, 4H), 2.69 (t, 2H), 3.18 (t, 2H), 3.28 (t, 2H), 3.70 (t, 4H),
4.14 (t, 2H), 5.06 (s, 2H), 5.83 (dd, 1H), 5.94 (d, 1H), 6.53 (d,
1H), 6.61 (d, 1H), 6.88-6.95 (m, 3H), 7.10 (d, 1H), 7.15 (t,
1H)
EXAMPLE 251
N-{2-methyl-3-[2-oxo-4-(2-thiophen-2-yl-ethoxy)-2H-pyridin-1-ylmethyl]-phe-
nyl}-methanesulfonamide
[0609] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 2.15 (s, 3H), 2.95
(s, 3H), 3.30 (t, 2H), 4.17 (t, 2H), 5.01 (s, 2H), 5.97 (dd, 2H),
6.03 (d, 1H), 6.74 (d, 1H), 6.89-6.96 (m, 2H), 7.01 (d, 1H), 7.09
(t, 1H), 7.16 (dd, 1H), 7.28 (t, 1H), 7.60 (br s, 1H)
EXAMPLE 252
1-(3-amino-2-methyl-benzyl)-4-[2-(4-bromo-thiophen-2-yl)-ethoxy]-1H-pyridi-
n-2-one
[0610] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 1.99 (s, 3H), 3.22
(t, 2H), 3.69 (br s, 2H), 4.10 (t, 2H), 5.04 (s, 2H), 5.83 (dd,
1H), 5.92 (d, 1H), 6.55 (d, 1H), 6.68 (d, 1H), 6.80 (s, 1H), 6.91
(d, 1H), 6.98-7.06 (m, 2H)
EXAMPLE 253
1-(6-chloro-benzo[1,3]dioxol-5-ylmethyl)-4-(2-pyrrol-1-yl-ethoxy)-1H-pyrid-
in-2-one
[0611] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 4.15 (t, 2H), 4.25
(t, 2H), 5.07 (s, 2H), 5.85-5.90 (m, 2H), 5.94 (s, 2H), 6.15-6.16
(m, 2H), 6.60-6.72 (m, 2H), 6.79 (s, 1H), 6.83 (s, 1H), 7.18 (d,
1H)
EXAMPLE 254
1-(6-chloro-benzo[1,3]dioxol-5-ylmethyl)-4-(2-thiophen-2-yl-ethoxy)-1H-pyr-
idin-2-one
[0612] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 3.26 (t, 2H), 4.12
(t, 2H), 5.06 (s, 2H), 5.89-5.92 (m, 4H), 6.78-6.94 (m, 4H),
7.14-7.18 (m, 2H)
EXAMPLE 255
1-[2-methyl-3-(2-pyrrolidin-1-yl-ethylamino)-benzyl]-4-(2-thiophen-2-yl-et-
hoxy)-1H-pyridin-2-one
[0613] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 1.78 (br s, 4H),
1.98 (s, 3H), 2.55 (br s, 4H), 2.79 (t, 2H), 3.23 (t, 2H), 3.28 (t,
2H), 4.14 (t, 2H), 4.33 (br s, 1H), 5.05 (s, 2H), 5.81-5.85 (m,
1H), 5.94 (d, 1H), 6.53 (d, 1H), 6.63 (d, 1H), 6.88-6.96 (m, 3H),
7.09-7.18 (m, 2H)
EXAMPLE 256
N-(2-{2-methyl-3-[2-oxo-4-(2-thiophen-2-yl-ethoxy)-2H-pyridin-1-ylmethyl]--
phenylamino}-ethyl)-acetamide
[0614] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 1.94 (s, 6H), 3.25
(t, 4H), 3.49 (q, 2H), 4.10 (t, 2H), 5.00 (s, 2H), 5.83-5.89 (m,
2H), 6.44 (d, 1H), 6.58 (d, 1H), 6.73 (t, 1H), 6.87-6.94 (m, 3H),
7.06 (t, 1H), 7.14 (d, 1H)
EXAMPLE 257
1-{2-methyl-3-[(pyridin-3-ylmethyl)-amino]-benzyl}-4-(2-thiophen-2-yl-etho-
xy)-1H-pyridin-2-one
[0615] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 2.03 (s, 3H), 3.28
(t, 2H), 4.14 (t, 2H), 4.42 (s, 2H), 5.07 (s, 2H), 5.86 (dd, 1H),
5.93 (d, 1H), 6.56 (d, 2H), 6.88-6.96 (m, 3H), 7.07 (t, 1H), 7.16
(dd, 1H), 7.30-7.34 (m, 1H), 7.73 (d, 1H), 8.54 (s, 1H), 8.64 (s,
1H)
EXAMPLE 258
2-methyl-3-[2-oxo-4-(2-thiophen-2-yl-ethoxy)-2H-pyridin-1-ylmethyl]-phenyl
ester
[0616] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 2.26 (s, 3H), 3.16
(s, 3H), 3.27 (t, 2H), 4.14 (t, 2H), 5.06 (s, 2H), 5.93-5.95 (m,
2H), 6.88-7.00 (m, 4H), 7.14-7.26 (m, 3H)
EXAMPLE 259
1-{2-methyl-3-[(pyridin-4-ylmethyl)-amino]-benzyl}-4-(2-thiophen-2-yl-etho-
xy)-1H-pyridin-2-one
[0617] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 2.07 (s, 3H), 3.28
(t, 2H), 4.14 (t, 2H), 4.44 (s, 2H), 5.08 (s, 2H), 5.86 (dd, 1H),
5.94 (d, 1H), 6.42 (d, 2H), 6.54 (d, 1H), 6.88-7.11 (m, 4H), 7.16
(dd, 1H), 7.30 (d, 2H), 8.55 (d, 2H)
EXAMPLE 260
1-{2-methyl-3-[(thiazol-4-ylmethyl)-amino]-benzyl}-4-(2-thiophen-2-yl-etho-
xy)-1H-pyridin-2-one
[0618] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 2.04 (s, 3H), 3.28
(t, 2H), 4.14 (t, 2H), 4.56 (s, 2H), 5.06 (s, 2H), 5.84 (dd, 1H),
5.94 (d, 1H), 6.55 (d, 1H), 6.65 (d, 1H), 6.88-7.20 (m, 6H), 8.85
(s, 1H)
EXAMPLE 261
1-[3-(4-methoxy-benzyloxy)-2-methyl-benzyl]-4-(2-thiophen-2-yl-ethoxy)-1H--
pyridin-2-one
[0619] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 2.15 (s, 3H), 3.29
(t, 2H), 3.81 (s, 3H), 4.16 (t, 2H), 4.99 (s, 2H), 5.08 (s, 2H),
5.88 (dd, 1H), 6.00 (d, 1H), 6.68 (d, 1H), 6.90-6.96 (m, 6H),
7.11-7.18 (m, 2H), 7.35 (d, 2H)
EXAMPLE 262
1-{3-[(3,5-dimethyl-isoxazol-4-ylmethyl)-amino]-2-methyl-benzyl}-4-(2-thio-
phen-2-yl-ethoxy)-1H-pyridin-2-one
[0620] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 1.98 (s, 3H), 2.26
(s, 3H), 2.37 (s, 3H), 3.28 (t, 2H), 4.04 (s, 2H), 4.15 (t, 2H),
5.07 (s, 2H), 5.85-5.95 (m, 2H), 6.62 (d, 1H), 6.74 (d, 1H),
6.88-6.96 (m, 3H), 7.14-7.19 (m, 2H)
EXAMPLE 263
1-(3-hydroxy-2-methyl-benzyl)-4-(2-thiophen-2-yl-ethoxy)-1H-pyridin-2-one
[0621] .sup.1H NMR (CDCl.sub.3+a few drop of CD.sub.3OD, 300 MHz)
.delta. 1.96 (s, 3H), 3.16 (t, 2H), 4.05 (t, 2H), 4.91 (s, 2H),
5.85-5.88 (m, 2H), 6.41 (d, 1H), 6.66 (d, 1H), 6.76-6.90 (m, 4H),
7.04 (d, 1H)
EXAMPLE 264
1-{2-methyl-3-[(1-methyl-pyrrolidin-2-ylmethyl)-amino]-benzyl}-4-(2-thioph-
en-2-yl-ethoxy)-1H-pyridin-2-one
[0622] .sup.1H NMR (CDCl.sub.3+a few drop of CD.sub.3OD, 300 MHz)
.delta. 1.57-1.67 (m, 3H), 1.79-1.89 (m, 6H), 2.25 (s, 3H),
2.47-2.50 (m, 1H), 2.98-3.04 (m, 2H), 3.13 (t, 2H), 4.01 (t, 2H),
4.88 (s, 2H), 5.78-5.81 (m, 2H), 6.32 (d, 1H), 6.47 (d, 1H),
6.73-6.85 (m, 3H), 6.94 (t, 1H), 7.00 (d, 1H)
EXAMPLE 265
1-{2-methyl-3-[2-(1-methyl-pyrrolidin-2-yl)-ethylamino]-benzyl}-4-(2-thiop-
hen-2-yl-ethoxy)-1H-pyridin-2-one
[0623] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 1.67-1.79 (m, 3H),
1.90-1.98 (m, 6H), 2.24 (q, 2H), 2.40 (s, 3H), 3.10-3.30 (m, 5H),
4.14 (t, 2H), 4.88 (br s, 1H), 5.04 (s, 2H), 5.82 (dd, 1H), 5.93
(d, 1H), 6.52 (d, 1H), 6.60 (d, 1H), 6.88-6.96 (m, 3H), 7.08-7.17
(m, 2H)
EXAMPLE 266
(2-{2-methyl-3-[2-oxo-4-(2-thiophen-2-yl-ethoxy)-2H-pyridin-1-ylmethyl]-ph-
enylamino}-ethyl)-phosphonic acid diethyl ester
[0624] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 1.32 (t, 6H), 2.02
(s, 3H), 2.10-2.20 (m, 2H), 3.28 (t, 2H), 3.42-3.53 (m, 2H),
4.07-4.17 (m, 6H), 5.06 (s, 2H), 5.85 (dd, 1H), 5.96 (s, 1H), 6.57
(d, 1H), 6.68 (d, 1H), 6.88-6.96 (m, 3H), 7.10-7.17 (m, 2H)
[0625] Preparation of 4-(isobutylthio)pyridine 1-oxide: A solution
of 5.80 g of isobutylthiol in 30 ml of DMF was stirred at room
temperature and 2.55 g of NaOMe was added. After 30 mins 6.0 g of
N-oxide was added and the reaction mixture was heated at reflux for
15 hours. The mixture was cooled, then solution was evaporated,
extracted with dichloromethane and subjected to silica gel column
chromatography (hexane/ethyl acetate) to obtain 5.8 g of
4-(isobutylthio)pyridine 1-oxide
[0626] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 0.99(s, 3H),
1.01(s, 3H), 1.85-1.89(m, 1H), 2.78(d, J=6.9 Hz, 2H), 7.04(d, J=7.2
Hz, 2H), 8.01(d, J=7.5 Hz, 2H)
[0627] Preparation of 4-(isobutylthio)pyridine-2(1H)-one: A mixture
of 500 mg of 4-(isobutylthio)pyridine-N-oxide, 5 ml of acetic
anhydride was heated at reflux for 10 hours. The mixture was
cooled, then added MeOH and 3N NaOH was added dropwise at pH
9.about.11 and stirred. After 1 hour solution was evaporated and 3N
HCl was added dropwise at pH6.5.about.7.5, extracted with ethyl
acetate and subjected to silica gel column chromatography
(hexane/ethyl acetate) to obtain the compound (90 mg).
[0628] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 1.05(s, 3H),
1.07(s, 3H), 1.95-2.00(m, 1H), 2.79(d, J=6.9 Hz, 2H), 6.19(dd, 1H),
6.31(s, 1H), 7.21(d, J=6.9 Hz, 1H)
EXAMPLE 267
4-(isobutylthio)-1-(2-methyl-3-nitrobenzyl)pyridin-2(1H)-one
[0629] Preparation of
4-(isobutylthio)-1-(2-methyl-3-nitrobenzyl)pyridine-2(1H)-one: A
mixture of 100 mg of 4-(isobutylthio)pyridine-2(1H)-one, 2 ml of
DMF, 65 mg of t-BuOK was stirred at room temperature and 105 mg of
2-methyl-3-nitrobenzyl chloride was added. After 3 hour, the
resulting solution was evaporated, extracted with dichloromethane
and subjected to silica gel column chromatography (hexane/ethyl
acetate) to obtain the compound (90 mg).
[0630] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 1.06(s, 3H),
1.08(s, 3H), 1.94-2.03(m, 1H), 2.42(s, 3H), 2.80(, J=6.9 Hz, 2H),
5.15(s, 2H), 6.07(dd, 1H), 6.35(s, 1H), 6.93(, J=7.5 Hz, 1H),
7.19-7.33(m, 2H), 7.71(, J=8.1 Hz, 1H)
EXAMPLES 268 TO 280
[0631] The procedure of Example 267 was repeated except the
starting material to obtain the titled compound.
EXAMPLE 268
1-(3-amino-2-methylbenzyl)-4-(isobutylthio)pyridin-2(1H)-one
[0632] A mixture of 400 mg of
1-(3-amino-2-methylbenzyl)-4-(isobuthylthio)pyridin-2(1H)-one, 5 ml
of ethyl alcohol, 3 ml of Raney nickel in water was stirred at room
temperature and 3.5 ml of NH.sub.2NH.sub.2H.sub.2O was added
dropwise. After 1 hour, the catalyst was removed by filtration
through Celite, and resulting solution was evaporated, extracted
with dichloromethane to obtain the title compound (200 mg).
[0633] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 1.01-1.07(m, 6H),
1.95-1.99(m, 1H), 2.13(s, 3H), 2.77(d, J=6.9 Hz, 2H), 5.07(s, 2H),
5.97(dd, 1H), 6.32(s, 1H), 6.70(d, J=7.8 Hz, 1H), 6.85-6.92(m, 2H),
7.08(t, J=7.8 Hz, 1H)
EXAMPLE 269
1-(3-amino-2-methylbenzyl)-4-(furan-2-ylmethylthio)pyridine-2(1H)-one
[0634] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 2.03(s,3H),
4.14(s,2H), 5.05(s,2H), 5.96(dd, 1H), 6.31(s, 2H), 6.45(d, J=7.8
Hz, 1H), 6.76(d, J=7.5 Hz, 1H), 6.88(d, J=6.9 Hz, 1H), 7.04(t,
J=7.8 Hz, 1H), 7.36(s, 1H)
EXAMPLE 270
1-(3-amino-2-methylbenzyl)-4-(pentylthio)pyridine-2-(1H)-one
[0635] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 0.89-0.93(m, 3H),
1.31-1.44(m, 4H), 1.66-1.73(m, 2H), 2.03(s, 3H), 2.85-2.90(m, 2H),
5.05(s, 2H), 5.92-5.95(m, 1H), 6.33(s, 1H), 6.60(d, J=7.2 Hz, 1H),
6.73(d, J=7.8 Hz, 1H), 6.85(q, 1H), 7.03(t, J=7.8 Hz, 1H)
EXAMPLE 271
1-(3-amino-2-methylbenzyl)-4-(phenethylthio)pyridine-2(1H)-one
[0636] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 2.13(s, 3H),
3.00(t, J=7.5 Hz, 2H), 3.16(t, J=7.5 Hz, 2H), 5.06(s, 2H),
5.94-5.97(dd, 1H), 6.39(s, 1H), 6.66(bs, 1H), 6.88(d, J=7.5 Hz,
2H), 7.06-7.10(m, 1H), 7.19-7.35(m, 3H)
EXAMPLE 272
1-(3-amino-2-methylbenzyl)-4-(butylthio)pyridine-2(1H)-one
[0637] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 0.95(t, J=7.2 Hz,
3H), 1.43-1.50(m,2H), 1.67-1.72(m,2H), 2.04(s, 3H), 2.89(t, J=7.3
Hz, 2H), 5.05(s, 2H), 5.94(dd, 1H), 6.33(s, 1H), 6.61(d, J=7.6 Hz,
1H), 6.75(d, J=8.1 Hz, 1H), 6.86(d, J=7.2 Hz, 1H), 7.04(t, J=7.6
Hz, 1H)
EXAMPLE 273
1-(3-amino-2-methylbenzyl)-4-(thiophen-2-ylmethylthio)pyridine-2(1H)-one
[0638] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 2.03(s, 3H),
4.34(s,2H), 5.04(s, 2H), 5.95(dd, 1H), 6.41(bs, 1H), 6.60(d, J=7.5
Hz, 1H), 6.75(d, J=7.5 Hz, 1H), 6.87-6.95(m, 2H), 7.01-7.05(m, 2H),
7.21-7.26(m, 1H)
EXAMPLE 274
1-(3-amino-2-methylbenzyl)-4-(pentylthio)pyridine-2(1H)-one
[0639] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 0.92(t, J=6.8 Hz,
3H), 1.32-1.46(m, 4H), 1.68-1.78(m, 2H), 2.43(s, 3H), 2.91(t, J=7.3
Hz, 2H), 5.15(s, 2H), 6.07(dd, 1H), 6.38-6.39(m, 1H), 6.94(d, J=7.2
Hz, 1H), 7.20-7.31(m, 2H), 7.72(d, J=8.1 Hz, 2H)
EXAMPLE 275
1-(3-amino-2-methylbenzyl)-4-(propylthio)pyridine-2(1H)-one
[0640] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 1.05(t, J=7.5 Hz,
3H), 1.71-1.78(m, 2H), 2.02(s, 3H), 2.87(t, J=7.3 Hz, 2H), 5.06(s,
2H), 5.94(dd, 1H), 6.33(d, J=1.8 Hz, 1H), 6.59(d, J=7.8 Hz, 1H),
6.70(d, J=7.5 Hz, 1H), 6.86(d, J=7.2 Hz, 1H), 7.03(t, J=7.8 Hz,
1H)
EXAMPLE 276
1-(3-amino-2-methylbenzyl)-4-(1-methylbutylthio)pyridine-2(1H)-one
[0641] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 0.93-1.02(m, 6H),
1.55-1.62(m, 2H), 1.68-1.75(m, 1H), 2.06(s, 3H), 2.89(t, J=7.5 Hz,
2H), 5.06(s, 2H), 5.94(dd, 1H), 6.33(s, 1H), 6.63(d, J=7.2 Hz, 1H),
6.78(d, J=8.1 Hz, 1H), 6.86(d, J=7.2 Hz, 1H), 7.04(t, J=7.6 Hz,
1H)
EXAMPLE 277
N,N-dimethyl-3-(2-methyl-3-((2-oxo-4-(2-(thiophen-2-yl)ethoxy)pyridin-1(2H-
)-yl)methyl)phenylamino)prop ane-1-sulfonamide
[0642] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 2.06(s, 3H),
2.23(t, J=6.8 Hz, 2H), 2.87(s, 6H), 3.06(t, J=7.2 Hz, 2H), 3.29(t,
J=6.5 Hz, 2H), 3.39(t, J=6.7 Hz, 2H), 3.62-3.68(m, 1H),
4.14-4.18(m, 2H), 5.06(s, 2H), 5.87(dd, 1H), 5.97(d, J=2.1 Hz, 1H),
6.60(d, J=7.5 Hz, 1H), 6.80(bs, 1H), 6.90(bs, 1H), 6.93-6.96(m,
2H), 7.10-7.18(m, 2H)
EXAMPLE 278
1-(3-nitro-2-methylbenzyl)-4-chloropyridin-2(1H)-one
[0643] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 2.38(s, 3H),
5.38(s, 2H), 6.54(dd, 1H), 7.27(d, J=7.8 Hz, 1H), 7.45(t, J=7.9 Hz,
1H), 7.79(d, J=7.8 Hz, 2H), 8.21(s, 1H)
EXAMPLE 279
1-(3-amino-2-methylbenzyl)-4-chloropyridin-2(1H)-one
[0644] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 1.94(s, 3H),
5.08(s, 2H), 6.23-6.28(m, 2H), 6.63(d, J=7.8 Hz, 1H), 6.90(t, J=7.8
Hz, 1H), 8.11(s, 1H)
EXAMPLE 280
1-(3-amino-2-methylbenzyl)-4-(2-(thiophene-2-yl)ethylamino)pyridine-2-(1H)-
-one
[0645] .sup.1H NMR (CDCl.sub.3, 300 MHz) .delta. 2.02(s, 3H),
3.07(t, J=6.8 Hz, 2H), 3.37(t, J=6.5 Hz, 2H), 4.97(s, 2H), 5.64(d,
J=8.1 Hz, 2H), 6.55(d, J=7.5 Hz, 1H), 6.75-6.83(m, 3H),
6.88-6.91(m, 1H), 7.00(t, J=7.5 Hz, 1H), 7.12(d, J=5.1 Hz, 1H)
TEST EXAMPLE 1
Minimum Inhibitory Concentration (MIC)
[0646] Antibacterial activities of the compounds synthesized in the
Examples were assessed by measuring their MIC values for standard
strains. Specifically, MIC value was measured by conducting the
following steps: diluting a test compound according to a two-fold
dilution method; dispersing the resulting dilution in a
Muller-Hinton agar broth; inoculating 2 ml of the standard strain
culture having a concentration of 10.sup.7 cfu (colony forming
unit)/ml; and incubating the mixture for 20 hrs at 37.degree. C.
The resulting MIC values were in the range of 128 to 0.2 .mu.g/ml,
preferably, 1 to 0.2 .mu.g/ml. These results reveal that the
compounds of the present invention have superior antibacterial
activity against various infectious bacterial strains including
MRSA strain.
* * * * *